Book / /C "*^ 2^ 
Copyiiglit]^? 



COPYRIGHT DEPOSIT. 



/ 

GENERAL PATHOLOGY /oo^ 

OR 

THE SCIENCE OF THE CAUSES, NATURE AND COURSE 
OF THE PROCESSES OF DISEASE 

BY 

DR. ERNST ZIEGLER 

PROFESSOR OF PATHOLOGICAL ANATOMY AND OF GENERAL PATHOLOGY 
IN THE UNIVERSITY OF FREIBURG IN BREISGAU 



TRANSLATED FROM 

THE TENTH REVISED GERMAN EDITION 

(gUSTAV FISCHER, JENA, 1901) 

AND EDITED 
BY 

ALDRED SCOTT WARTHIN, Ph.D., M.D. 

PROFESSOR OF PATHOLOGY AND DIRECTOR OF THE PATHOLOGICAL LABORATORY IN THE 
UNIVERSITY OF MICHIGAN. ANN ARBOR, MICHIGAN 



, 1p)rof usels f llustrateD 



NEW YORK 
WILLIAM WOOD AND COMPANY 

MDCCCCIII 



THE LIBRARY OF 
CONGRESS. 

Two Copies Recdiveci 

OCT 5 fq03 

-Copyright tdUy 
cuss Ol XXc. Nc 

^ ^ ^ 7 

COPY 3. ' 



Copyright, 1903 
WILLIAM WOOD AND COMPANY 



Rudolf Virchow 



IN AUFRICHTIQER VEREHRUNQ 
GEWIDMET 



AUTHOR'S PREFACE TO THE TENTH EDITION. 



1^5" the following pages of the tenth edition of my Text-book of Gen- 
eral Pathology and Pathological Anatomy are to be found the re- 
sults of two and twenty years of labor that has been but rarely inter- 
rupted. Since the first edition, which appeared in 1881, 1 have constantly 
endeavored to improve the book both in its contents as well as in its 
form ; and I believe that I dare commit myself to the hope that in this 
edition there is offered a work which, within its assigned limits, presents 
the most important achievements of the nineteenth century in the field 
of general pathology and pathological anatomy in such a form as to 
meet the needs of the practising physician as well as of the student, who 
through the study of such would acquire a scientific foundation for prac- 
tical medicine. 

He who to-day looks back upon the results of medical investigation 
during the nineteenth century finds his attention involuntarily fixed 
upon that investigator who for the full half of the century just passed 
has been constantly active, and who through his scientific labors and his 
teaching has pointed the way to the knowledge of morbid processes, their 
nature and their origin ; and in part has himself realized, and in part has 
paved the way and made possible the great advance of the past century 
in the domain of general pathology and pathological anatomy. There- 
fore it appears to me fitting in this year, in which the science of medi- 
cine of Germany and of the whole world is preparing to honor the 
eightieth birthday of its great master, Rudolf Yirchow, to dedicate to 
him this book as a duty of gratitude. May he thereby learn that also 
those to whom it was not granted to sit as students at his feet have 
striven to build further upon the foundation laid by him, and have seen 
in him their master, to whom they are attached in gratitude and venera- 
tion. 



In the revision of the new edition I have gone through each chapter 
with great care, and have supplemented, corrected, and extended the 
subject-matter according to the most recent literature and new investiga- 
tions of my own. 

The first three chapters have been completely worked over and 
reshaped, and I hope that by their new form and order the reader will be 



vi author's preface to the tenth edition. 

enabled to orient the conditions there considered more easily than was the 
case in former editions. 

In spite of the criticisms directed against certain portions of my 
presentation of inflammation and tumors I have not been led to make 
any changes touching the essential contents of these chapters. The 
attacks directed against these have inclined rather to strengthen my 
standpoint than to weaken it ; although I have been induced, by chang- 
ing somewhat the formulation of my views, to meet certain strictures 
which were caused more by the form of presentation than by the content 
itself. 

Czerny's support of the theory of the parasitic nature of true tumors 
has not changed my view as to their etiology and nature, and if I have 
altered the phrase ^hieiv -formation of tissue icMch is not caused by infection 
to new formation of tissue appay^ently arising independently,''^ I have done 
so, as is shown by the subsequent text, not because of any doubt in the 
correctness of the former expression, but for the purpose of avoiding 
the criticism that such a definition might have a retarding influence upon 
investigations as to tlie etiology of tumors. 

I have given especial attention to the revision of the chapters on 
Vegetable and Animal Parasites, and have enriched these with new and, 
I hope, instructive illustrations. It may be argued as to whether it is 
necessary in a text-book on general pathology to go so far into the sepa- 
rate forms of parasitic diseases as I have done ; and whether it would not 
be better to be content with what is said in the first and third chapters 
upon Infection and the Resisting Powers of the Organism. For the 
acquiring c-f an understanding as to what an infection is and how the 
organism in general behaves toward it, the latter would probably suffice; 
but it appears to me to meet a pressing need that the student, after he 
has learned to recognize the pathological processes of life, should then be 
instructed more closely regarding the properties of the parasites causing 
the different infections, their manner of action upon the different tissues 
and the organism as a whole, and their mode of spreading throughout 
the body. For the elucidation of these conditions of so great importance 
to the physician I have provided this chapter with numerous illustra- 
tions, particularly the sections treating of Streptococcus pyogenes^ Staphy- 
lococcus pyogenes aureus, and Tuberculosis, as well as those treating of the 
pathogenic Protozoa. 

The bibliography has been brought up to the end of 1900, and I have 
endeavored in so far as possible to cite those investigations which are 
adapted to facilitate and advance scientific research in the given field. 
Since such collections of the literature as may be easily utilized are want- 
ing, I believe the bibliography given has met a pressing want, and I 
have already had the satisfaction of knowing that this has been recog- 
nized on various sides. 

I cannot neglect to remember with gratitude in this edition the pub- 



author's preface to the tenth edition. 



vii 



lisher, Dr. Gustav Fischer. To the excellent form which he has given 
the book in all the editions is owing a large part of its success. His 
friendly and obliging spirit has made it possible to provide the book 
with such illustrations as are suitable to explain and to amplify that 
which is described in the text. E. Ziegler. 

Freiburg im Breisgau, April, 1901. 



TRANSLATOR'S PREFACE. 



IN" the translation of the tenth edition of Ziegler 's General Pathology ^' 
the endeavor of the translator has been to render the text and spirit 
of the original in a simple and consistent English form, suitable to 
the needs of the medical student and reader. He has refrained from 
alterations of the subject-matter, and has made but few additions, the 
latter being only of such a nature as to adapt certain statements made in 
the text the better to their American environment. The dedication of the 
German edition to Yirchow has made the book in a certain sense a Vir- 
chow^' Festschrift^'; and it seems especially fitting that it should contain 
the bibliography of the most important achievements of the past half- 
century in the domain of pathology and pathological anatomy. The 
bibliography of the earlier editions was omitted in the previous transla- 
tions, but in the present translation the complete bibliography, as given 
by Ziegler, has been included. In addition the editor has inserted some 
of the most important American references, particularly those of the 
last several years. He has not in any measure attempted to make a fully 
representative American bibliography, but has chosen those references 
which he has found of most service in his teaching. It is not necessary 
here to emphasize the teaching value of such a bibliography as given in 
the present volume. In the study of a science in which such great ad- 
vances are almost daily made, and in which the point of view changes 
at a corresponding rate, it seems essential that the student, in addition 
to a thorough grounding in the established principles, should be given 
also a broader view of the development and solution of pathological 
problems. 

Aldeed Scott Warthin. 

Ann Arbok, Michigan, September 1st, 1903. 

Note. — Because of the diiference in the size of the page it has been found necessary 
to reduce slightly some of the illustrations. In such cases the magnification or amplifi- 
cation has been changed to meet the amount of reduction. 



CONTENTS. 



PAGE 

Introduction 1 

CHAPTER I. 
Extrinsic and Intrinsic Causes of Disease. 

1. Origin of Disease through Extrinsic Causes, 5 

1. Origin of Disease through Deicient Supply of Food and Oxygen, 

through Fatigue, Heat, and Cold, Changes of Atmospheric Press- 
ure and Electrical Influences, 5 

2. The Origin of Disease through Mechanical Influences, . . . .15 

3. The Origin of Disease through Intoxication, 18 

4. The Origin of Disease through Infection or Parasitism. Miasms, and 

Contagions. Vegetable and Animal Parasites, . . . .31 
II. The Intrinsic Causes of Disease. Predisposition, Idiosyncrasy and Immu- 
nity. Inheritance of Pathological Conditions and Diseases, . . .47 

CHAPTER II. 

The Spread and Generalization of Disease Throughout the Organism. 
Autointoxications and Secondary Diseases. 

I. Metastasis and Embolism and their Significance in the Etiology of L3^m- 



phogenous and Haematogenous Diseases, 66 

II. Secondary Local and General Diseases. Autointoxication. Diseases caused 

through Disturbances or Cessation of Gland-functions, . . . .75 
III. Fever and Its Significance, .92 



CHAPTER III. 

The Protective and Healing Forces of the Human Body. The Acquiring 

OF Immunity. 

I. The Natural Protective Contrivances, Protective Forces, and Healing Powers 

of the Human Organism, and their Action, 99 

II. The Acquiring of Immunity against Infection and Intoxication. Protection 

through Inoculation, Ill 

CHAPTER IV. 

Disturbances in the Circulation of the Blood and of the Lymph. 

I. General Disturbances of the Circulation Dependent upon Changes in the 
Function of the Heart, Changes in the General Vascular Resistance, and 



Changes in the Mass of the Blood, 128 

II. Local Hyperaemia and Local Anaemia, 129 

III. Coagulation, Thrombosis, and Stasis, 134 

IV. CEdema, . . .150 

V. Haemorrhage and the Formation of Infarcts, . . . . ... . 156 

VI. Lympborrhagia, 163 



xii 



CONTENTS. 



CHAPTER V. 

PAGE 

Retrograde Disturbances of Nutrition and Infiltrations of Tissues. 
I. General Considerations Concerning the Retrograde Disturbances of Nutrition 



and the Tissue-intiltrations, 165 

II. Death of the Organism, 166 

III. Necrosis, 169 

IV. Hypoplasia, Agenesia, and Atrophy, 178 

V. Cloudy Swelling and Hydropic Degeneration, . . , . . . 188 

VI. Lipomatosis, Atrophy of Fat-tissue, and Fatty Degeneration, . . . 190 

VII. The Deposit of Glycogen, . . .199 

VIII. Mucous Degeneration, 201 

IX. Formation of Epithelial Colloid and Epithelial Hyaline Concretions, . . 203 

X. The Pathological Cornification of Epithelium, 206 

XI. Amyloid Degeneration and the Amyloid Concretions, ..... 208 

XII. Hyaline Degeneration of Connective Tissue, and the Hyaline Products of 

Connective-tissue Cells, 215 

XIII. Petrifaction of the Tissues and the Formation of Concretions and Calculi, . 220 

XIV. The Pathological Formation of Pigment, 231 

XV. The Pathological Absence of Pigment, 250 

XVI. The Formation of Cysts, 251 



CHAPTER VI. 

Hypertrophy and Regeneration. Results of Transplantation. Metaplasia. 

I. General Considerations Concerning the Processes Known as Hypertrophy and 

Regeneration, and the Accompanying Cellular Changes, .... 255 
II. The Processes of Hyperplasia and Regeneration in the Various Tissues, . 280 

III. The Results of Transplantation and Implantation of Tissues and Organs, . 305 

IV. The Metaplasia of Tissues, 310 



CHAPTER VII. 
Inflammation. 

I. The Early Stages of Acute Inflammation, 314 

II. The Termination of Acute Inflammation in Healing, 341 

III. The Inflammatory New-formation of Tissue, Substitution of Exudates and 

Tissue-necroses by Connective Tissue, 343 

IV. Phagocytosis Occurring in the Course of Inflammations, and the Formation 

of Foreign-body Giant-cells, 356 

V. Chronic Inflammations, 360 



CHAPTER VIII. 
Tumors. 

I. General Considerations, 366 

II. The Different Forms of Tumors, , 380 

1. Tumors Derived from Connective Tissue or the Supporting Frame- 
work, 380 

(a) Fibroma, 380 

(b) Myxoma, 382 

(c) Lipoma, 384 

(d) Chondroma, 386 

(e) Osteoma, 389 

(/) H^Bmangioma and Lymphangioma, 393 



CONTENTS. xiii 

PAGE 

{g) Myoma, 404 

\h) Glioma and Neuroglioma Ganglionare, 408 

(^■) Neuroma and Neurofibroma, 411 

{k) Sarcoma, 414 

2. The Epithelial Tumors, 433 

{o) General Remarks, 433 

{h) Papillary Epithelioma, Adenoma, and Cystadenoma, . . . 434 
(c) Carcinoma and Cystocarcinoma, 449 

3. The Teratoid Tumors and Cysts, .473 

CHAPTER IX. 

Disturbances of Development and the Resulting Malformations, 

I. General Considerations Regarding Disturbances of Development and the Ori- 
gin of Malformations, 488 

II. The Different Forms of Malformations in Man, 496 

1. Arrests of Development in a Single Individual, 496 

{a) Arrest of the Development of the Entire Embryonal Anlage, . 496 
(6) Defective Closure of the Cerebrospinal Canal and the Accom- 
panying Malformations of the Nervous System, . . . 498 

(c) The Malformations of the Face and Neck, 508 

{d) Faulty Closure of the Abdominal and Thoracic Cavities and the 

Accompanying Malformations, 511 

{e) Malformations of the External Genitalia and Anus, due to Ar- 
rested Development, 514 

(/) Malformations of the Extremities, due to Arrested Development, 516 

2. Abnormal Position of the Internal Organs and of the Extremities, . 520 

3. Malformations, due to Excessive Grov^^th or Multiplication of Organs 

or Body-parts, 522 

4. True and False Hermaphrodism, 526 

5. Double Monsters, 531 

(a) Classification of Double Monsters, 531 

{h) The Chief Forms of Double Monsters, . . . . • .531 

CHAPTER X. 

The Parasitic Fission-fungi and the Diseases Caused by Them. 

I. General Considerations Regarding the Schizomycetes or Fission-fungi, . 540 

1. General Morphology and Biology of the Fission -fungi, , . . 540 

2. General Considerations Concerning the Pathogenic Schizomj^cetes and 

their Behavior in the Human Organism, 551 

II. The Different Forms of Bacteria and the Infectious Diseases Caused by 

Them, .... . 559 

1. The Cocci or Spha^robacteria and the Morbid Processes Caused by 

Them, . . .559 

{a) General Considerations Regarding the Cocci, .... 559 
{b) Pathogenic Cocci, 561 

2. The Bacilli and the Polymorphous Bacteria and the Pathological Proc- 

esses Produced by Them, 580 

{a) General Considerations Regarding Bacilli and the Polymorphous 

Bacteria, 580 

(5) The Pathogenic Bacilli and Polymorphous Bacteria, . . . 584 

3. The Spirilla and the Diseases Caused by Them, 659 

{a) General Remarks upon the Spirilla, 659 

ih) The Pathogenic Spirilla 660 



CHAPTER XI. 

The Yeasts and Moulds and the Diseases Produced by Them, . . . 668 



XIV CONTENTS. 



CHAPTER XII. 
The Animal Parasites and the Diseases Pkoduced by Them. 



PAGE 

I. Protozoa, 680 

II. Vermes. Worms, 700 

A. Platyhelmintlies. Flat-Worms, 700 

1. Trematoda. Sucking-- Worms, 700 

2. Cestoda. Tape -Worms, 705 

B. Nemathelminthes. Round-Worms, . 718 

III. Arthropoda, «... 731 

1. Arachnida, . .731 

2. Insecta, 735 

Index, 739 



LIST OF ILLUSTRATIONS. 



PAGE 

1. Lightning-figures on the shoulder, breast, and arm 14 

2. Multiple emboli in the branches of the pulmonary artery 67 

3. Fat-embolism of the lungs 68 

4. Fat-embolism of the kidney 69 

5. Thy reoprival cachexia 85 

6. Myxoedema 86 

7. Same case after treatment with thyroid extract 86 

8. Female cretin 87 

9. Temperature chart of a continuous remittent fever 93 

10. Temperature chart of a continued fever with rapid rise and fall 94 

11. Temperature curve of an intermittent fever 94 

12. Recent haemorrhagic infarct of the lung 134 

13. Bundles and stellate clusters of fibrin threads or rods 136 

14. Red thrombus 136 

15. Laminated mixed thrombus rich in cells 137 

16. White thrombus poor in cells 137 

17. Rapid blood-stream 138 

18. Moderately slow blood-stream 138 

19. Greatly retarded blood-stream 138 

20. Thrombus-formation in heart 143 

21. Thrombosis of femoral vein 144 

22. Remains of a thrombus of femoral vein 145 

23. Obliteration of pulmonary artery by connective tissue 146 

24. Remains of embolic plugs in pulmonary artery 146 

25. Embolism of intestinal artery with purulent arteritis 147 

26. Stasis from venous hypercEmia 149 

27. (Edema of muscle 151 

28. Hgemorrhage into skin 156 

29. Peripheral portion of an anaemic infarct of kidney 161 

30. Recent haemorrhagic infarct of lung 162 

31. Necrosis of kidney epithelium 170 

32. Coagulation-necrosis of mesenteric lymph-gland 172 

33. Waxy necrosis of striped muscle 173 

34. Caseation-necrosis of tuberculous focus 173 

35. Fibrin -containing tubercle of the lung 174 

36. Liquefaction-necrosis 175 

37. Dry gangrene of the toes 176 

38. Skeleton of a female cretin, thirty-one years of age 179 

39. Skeleton of a female dwarf, fifty-eight years of age 179 

40. Head of Helene Becker (microcephalia) 180 

41. Brain of Helene Becker 180 

42. Hypoplasia and microgyria of left cerebral hemisphere 180 

43. Hypoplasia of uterus 181 

44. Hypoplasia of the small intestine 181 

45. Sections of ovary at different ages c 182 

46. Juvenile muscular atrophy 183 

47. Excentric atrophy of lower end of tibia and fibula 184 

48. Senile atrophy of skull-cap 185 

49. Section through atrophic muscle 185 

50. Senile atrophy of the kidney 186 

51. Arteriosclerotic contracted kidney 186 

52. Pressure-atrophy of spinal column 187 

53. Hemiatrophia facialis 187 

54. Cloudy swelling of liver-cells 188 



XVI 



LIST OF ILLUSTRATIONS. 



PAGE 



55. Cloudy swelling of kidney-cells 189 

56. Hydropic degeneration of carcinoma-cells 190 

57. Hydropic degeneration of muscle-fibres 190 

58. Transverse section of hydropic muscle 190 

59. Fatty infiltration of liver 191 

60. Lipomatosis of calf -muscles 192 

61. Spinal muscular atrophy with lipomatosis 192 

62. Fat-containing liver-cells 194 

63. Fatty degeneration of heart-muscle 194 

64. Marked chronic fatt}'" degeneration of heart 195 

65. Fatty degeneration of kidney epithelium 195 

66. Fatty degeneration, vacuolar degeneration and necrosis of heart-muscle 196 

67. Fat-granule cells : 196 

68. Cholesterin plates and margarin needles 199 

69. Mucoid degeneration of epithelial cells 201 

70. Mucoid degeneration of epithelial cells, from a cystadenoma of ovary 202 

71. Mucoid degeneration of connective tissue 202 

72. Colloid degeneration of thyroid 203 

73. Secretion of colloid in the thyroid 203 

74. Urinary tubules filled with colloid 204 

75. Colloid concretions 204 

76. Hypertrophic prostate with concretions 205 

77. Amyloid spleen 208 

78. Amyloid liver treated with iodine 209 

79. Amyloid degeneration of splenic follicles and splenic pulp 210 

80. Amyloid liver 211 

81. Amyloid kidney 212 

82. Corpora amylacea 214 

83. Hyaline degeneration of the connective tissue of a colloid goitre 216 

84. Hyaline degeneration of connective tissue in a tuberculous bursa 216 

85. Hyaline degeneration of blood-vessels 217 

86. Hyaline degeneration of the connective tissue of the myocardium 217 

87. Sclerosis and calcification of a uterine artery 220 

88. Calcification of the media of the aorta 221 

89. Calcified cerebellar vessels 221 

90. Calcification of epithelium of urinary tubules 221 

91. Concretions of lime salts 222 

92. Section of psammoma of dura mater 222 

93. Deposit of urates in knee-joint 224 

94. Deposit of needle-shaped cr^'stals of sodium urate 224 

95. Gouty nodules of hand 225 

96. Faceted stones from gall-bladder 226 

97. Section of cholesterin stone 227 

98. Uric-acid infarction of kidney 227 

99. Coral-like urinary calculus 228 

100. Calculi of sodium urate and ammonium-magnesium phosphate 228 

101. Incrusted lead-pencil from bladder 229 

102. Large hairy na)vus on back and buttocks 231 

103. Pigmented cells from skin in Addison's disease 232 

104. Cells containing amorphous pigment. Crystals of hsematoidin 236 

105. Hsemosideriu- and hoematoidin-containing cells 237 

106. Deposit of pigment-cells in a lymph-gland 238 

107. Infiltration of liver-rods with ha?mosiderin 239 

108. Hsemachromatosis of the liver 240 

109. Hoemosiderosis of the bone-marrow 241 

110. Hsematogenous ha}mosiderosis of kidney of pernicious malaria 242 

111. Icterus of liver due to compression of common duct 244 

112. Icterus of kidney 246 

113. Deposit of cinnabar in tattoo 248 

114. Argyria of rabbit's kidney 249 

115. Vitiligo endemica 250 

116. Multiple cysts in epididymis 252 

117. Dilatation cyst of pancreas 252 

118. Hydrops tubse 253 

119. Elephantiasis femorum neuromatosa 255 

120. Elephantiasis cruris lymphangiectatica 256 



LIST OF ILLUSTRATIONS. Xvii 

PAGK 

121. Ichthyosis congenita (microscopical) 256 

122. Ichthyosis congenita 257 

123. Cornu cutaneum from back of hand , 257 

124. Cornu cutaneum from arm 257 

125. Head of a bearded woman 258 

126. Leontiasis ossea 258 

127. Hypertrophy of left ventricle 260 

128. Hypertrophy of incisor- tooth of a white rat, due to disuse 261 

129. Elephantiasis scroti 261 

130. Acromegaly 262 

131. Skeleton of hand from case of acromegaly 263 

132. Cutaneous portion of a laparotomy wound. 266 

133. Healing of intestinal ulcer 267 

134. Scar of muscle and tendon 268 

135. Edge of embolic scar 269 

136-144. Nuclear changes in cell-division 273-274 

145. Atypical karyokinetic figures 275 

146-149. Giant-cells from an osteosarcoma 276 

150. Proliferating adipose tissue 276 

151-157. Nuclear changes in cell-division 277-278 

158. Regeneration of the epithelium of the bile-ducts 281 

159. Healing blister 281 

160. Development of blood-vessels 284 

161. Two vessels of papillary body, with proliferation of endothelium 285 

162. Proliferating periosteum four days after fracture of bone 286 

163. Isolated cells from wound-granulation 287 

164. Development of connective tissue from fibroblasts 287 

165. Scar from skin, two years old. 288 

166. Periosteal formation of cartilage 288 

167. Myelogenous formation of bone from osteoblasts 289 

168. Formation of osteoid trabeculse in the proliferating periosteum 289 

169. Formation of bone upon old bone by deposits of osteoblasts 290 

170. Section from a germ-centre of a mesenteric lymph-gland 293 

171. Regeneration of striped muscle. 297 

172. Sclerotic tissue from the posterior columns of spinal cord 300 

173. Old and newly formed nerve-fibres 301 

174. Cross-section of nerve-bundle from median nerve four months after wound. . . 301 

175. Amputation-neuroma 302 

176. Skin-transplantation of about four and a half days 307 

177. Metaplasia of cartilage into reticular tissue 311 

178. Formation of bone from cartilage in a callus 312 

179. Formation of bone from connective tissue 312 

180. Inflamed human mesentery 317 

181. Meningitis recens purulenta 322 

182. Hfematogenous staphylococcus myositis 322 

183. Section through the edge of a blister 323 

184. Parenchymatous hepatitis 323 

185. Mucous catarrh of a bronchus 324 

186. Purulent desquamative catarrh of trachea 326 

187. Catarrhal secretions of different mucous membranes 327 

188. Acute haemorrhagic-fibrinous inflammation of trachea 328 

189. Croupous membrane from trachea 328 

190. Section of diphtheritic membrane 329 

191. Croupous tracheitis 330 

192. Traumatic fibrino-purulent peritonitis 330 

193. Fibrinous pleuritis 330 

194. Fibrino-purulent diplococcus pleuritis 331 

195. Croupous pneumonia 332 

196. Purulent bronchitis, peribronchitis, and peribronchial bronchopneumonia. . . . 334 

197. Section of a pock pustule 334 

198. Embolic abscess of intestinal wall 335 

199. Suppuration and necrosis of the mucosa of the intestine in dysentery 336 

200. Phlegmon of subcutaneous tissue 337 

201. Necrosis of the epithelium of the epiglottis 338 

202. Bacillary diphtheritis of colon in dysentery 339 

203. Section of uvula in diphtheria 339 



xvm 



LIST OF ILLUSTKATIOXS. 



PAGE 

204. Diphtheritic necrosis of a nieseuteric lymph-glaud 340 

205. Isolated cells from a wound-granulation 344 

206. Cross-section of blood-vessel from the deeper layers of the skin 344 

207. Granulation tissue from open wound 345 

208. Healing of incised wound of skin 347 

209. Cutaneous portion of a laparotomy scar 348 

210. Beginning organization of pericardial exudate 349 

211. Granulation-tissue formation on the pleura in pleuritis 349 

212. Organization of pericardial exudate . , 350 

213. Intraseptal and iutra-alveolar development of connective tissue in the lutig. . . 350 

214. Development of formative tissue in a thrombosed femoral artery 351 

215. Edge of fresh hnemorrhagic infarct of lung 351 

216. Edge of organizing ha?morrhagic infarct of lung 352 

217. Fibroid area in heart-muscle 353 

218. Granule-cells in a focus of degeneratiou of the brain 356 

219. Phagocytes from granulation tissue 357 

220. Collection of pigment-granule cells in a lymph-gland 357 

221. Dog's hair encapsulated in subcutaneous tissue 358 

222. Kecrosis in lower portion of femur 360 

223. Changes in luns; and pleura in chronic purulent pleuritis 361 

224. Stone-cutter's lung 362 

225. Condyloma acuminatum 362 

226. Periosteal hyperostosis of the tibia 363 

227. Section through mucosa of atiophic colon , 364 

228. Indm-atiou and atrophy of kidney tissue in chronic nephritis 364 

229. Hyperplasia of connective tissue and proliferation of bile-ducts la chronic 

hepatitis 365 

230. Tissue from mammary cancer with many division-figures *. . 367 

231. Fungoid carcinoma of body of uterus 368 

232. Papillary adenoma of rectum 368 

233. Primary carcinoma of gall-bladder 372 

234. Primary carcinoma of liver 375 

235. Metastases in periglandular lymph- vessels of axillary region 376 

236. ]\[etastases of carcinoma in portal vein and liver capillaries 376 

237. Metastatic sarcoma of liver 377 

238. Recurrent sarcoma of femur 378 

239. Hard fibroma of ear-lobe 380 

240. Section of a?dematou8 fibroma of uterus 380 

241. Fibroma pericanaliculare mamma? 381 

242. Cells from a myxoma of the periosteum 383 

243. Section of a myxosarcoma 383 

244. Lipoma of the shoulder region 384 

245. Lipomyxoma of the back 385 

246. Periosteal chondroma of finger-phalanx 386 

247. Section of chondroma of ribs 386 

248. Chondromyxosarcoma parotidis 387 

249. Periosteal chondroma of calcaneus 387 

250. Osteochondroma of humerus .388 

251. Ivory-like exostosis of parietal bone 389 

252. Exostosis cartilaginea of tibia 390 

253. Ivory-like osteoma of parietal bone 391 

254. Osteoma of dura mater 391 

255. Osteochondroma of humerus 392 

256. Teleangiectasis of abdominal panniculus 393 

257. Dilated capillaries from a teleangiectatic tumor of the brain 394 

258. Angioma cavernosum cutaneum congenitum 394 

259. Angioma cavernosum hepatis 395 

260. Angioma simplex hypertrophicum 396 

261. Angioma simplex hypertrophicum cutaneum et subcutaueum 396 

262. Angioma cavernosum hypertrophicum 397 

263. Angioma arteriale plexiforme 398 

264. Weeping subepithelial lymphangioma of skin 399 

265. Lymphangioma cavernosum subcutaneum 400 

266. Large hairy pigmented naevus 401 

267. Lymphangioma hypertrophicum 401 

268. Lymphangioma hypertrophicum 402 



LIST OF ILLUSTRATIONS. xix 

PAGE 

269. Section through two papillae of a fleshy wart 402 

270. Myoma of uterus 404 

271. Angiomyoma subcutaneum dorsi 405 

272. Cells from rliabdomyomata ' 406 

273. Glioma cerebri 408 

274. Section of a glioma cerebri 409 

275. Neuroglioma ganglionare 410 

276. Amputation neuroma of sciatic nerve 412 

277. Nerves from a cirsoid neuroma 413 

278. Cirsoid neuroma of sacral region. . . 413 

279. Sarcoma of intermuscular septa of cervical muscles 416 

280. Lymphosarcoma of nasal mucosa 416 

281. Large round-celled sarcoma of skin 417 

282. Sarcoma of mamma 417 

283. Spindle-cells from a large spindle-celled sarcoma of cheek 418 

284. Cells from a myelogenous giant-cell sarcoma 418 

285. Giant-cell sarcoma of upper jaw 419 

286. Endothelioma of pia mater 421 

287. Endothelioma durfE matris 422 

288. Endothelioma of pleura 422 

289. Endothelioma of mamma 423 

290. Haemangioendothelioma of kidney 424 

291. Angiosarcoma of thyroid 425 

292. Angiosarcoma of testicle 425 

293. Chondrofibroma of parotid 426 

294. Melanotic alveolar sarcoma of skin 427 

295. Melanotic sarcoma of skin 428 

296. Metastasis of a melanotic sarcoma of skin 429 

297. Osteoid sarcoma of the ethmoid bone 429 

298. Petrifying large-celled sarcoma of tibia 430 

299. Section of a psammoma of dura mater 430 

300. My xoangiosarcoma of parotid 431 

301. Papillary epithelioma 433 

302. Senile horny wart 434 

303. Papillary epithelioma of larynx 435 

304. Papillary epithelioma of bladder 435 

305. Papillary epithelioma of bladder 436 

306. Adenoma tubulare of intestine 438 

307. Adenoma tubulare of stomach 438 

308. Adenoma mammae tubulare 439 

309. Adenoma mammae alveolare 439 

310. Adenoma renum tubulare papilliferum 440 

311. Fibroma intercanaliculare mammae 441 

312. Section of cystadenoma ovarii papilliferum 442 

313. Adenocystoma of bile-ducts 443 

314. Portion of a multilocular adenocystoma of the ovary 443 

315. Section of an adenocystoma of testicle 443 

316. Multilocular adenocystoma of liver 444 

317. Cystoma of kidney -. 444 

318. Adenocystoma ovarii partim simplex partim papilliforum 445 

319. Portion of an adenocystoma papilliferum ovarii 445 

320. Cystoma papilliferum ovarii 446 

321. Papillary adenocystoma of ovary 447 

322. Papillary cystoma of breast 448 

323. Section of carcinoma of the lip 454 

324. Beginning cancer of portio vaginalis uteri 455 

325. Development of adenocarcinoma of colon 456 

326. Developing adenocarcinoma of stomach 456 

327. Cystocarcinoma of mamma 457 

328. Tubular adenoma of mamma with beginning carcinoma 457 

329. Carcinoma placentare of uterus 458 

330. Horny carcinoma of tongue 460 

331. Epithelial plug from a cancer of the skin 460 

332. Adenocarcinoma recti tubulare 461 

333. Adenocarcinoma fundi uteri 461 

334. Carcinoma simplex mammae 462 



XX 



LIST OF ILLUSTRATIONS. 



PAGE 

335. Acinous carcinoma of mamma 462 

836. Tubular scirrhous cancer of breast 463 

887. Segment of a cancer of breast 464 

888. Mucoid carcinoma of breast , 465 

839. Development of a mucoid cancer in atrophic gastric mucosa 465 

340. Carcinoma mucosum mammce 466 

841. Carcinoma with hyaline drops *. 466 

343. Enlarged hydropic cancer cells 467 

848. Carcinoma myxomatodes 467 

844. Adenosarcoma malignum of kidney 468 

845. Cystocarcinoma papilliferum mammje 469 

846. Cystocarcinoma papilliferum ovarii 470 

347. Papillar}'' cystocarcinoma of mammae 470 

348. Colloid carcinoma of thyroid 471 

349. Section of enlarged axillary lymph-gland with beginning metastases of carci- 

noma 472 

350. Metastatic cancer-cell in liver-capillary 473 

851. Metastatic cancer in liver from primary carcinoma of the pancreas 473 

852. Spina bifida occulta with a myolipoma 474 

858. Adenoma-like suaring-oli of portions of mucosa of small intestine 476 

854. Adenoma-liUe remains of Wolffian body in the uterine wall 477 

355. Portion of the wall of a dermoid cyst of the ovary 482 

356. Section of a prominence in a multilocular dermoid 483 

857. Congenital adenoc3'stoma of testicle 484 

• 358. Teratoma of testicle 485 

359. ^Malformation of head due to amniotic adhesion 489 

860. Malformation of face due to amniotic adhesion 490 

361. Hand stunted by amniotic adhesion 491 

362. Deformity and stunting of hand due to pressure 491 

368. Hydatid mole 496 

364. Lithopa!dion 497 

365. Craniorachischisis 499 

366. Spina bifida sacralis 500 

367. Myelomeningocele sacralis 501 

368. Anencephalia et acrania 504 

869. Cranioschisis with exencephalus 504 

870. Partial agenesia of the cranium 504 

371. H3'drencephalocelc occipitalis 505 

872. Encephalomcningocele naso frontalis 505 

378. Synophthalmus or cyclopia 506 

374. Frontal section of cranial cavity in synophthalmus microstomus 506 

875. Wolf's jaws 509 

376. Agnathiaand synotia 509 

377. Hernia funiculi umbilicalis. 512 

378. Fissura abdominis et vesica? urinaria? 513 

379. Hypospadias 514 

380. Epispadias 514 

881. Complete absence of urethra and external genitals .... 515 

382. Amelus 517 

383. ]\Iicromelus 517 

884. Sympusapus 517 

385. Sympus dipus 517 

886. Defect of femur and fibula 518 

•387. Perodactylism and syndactylism 518 

888. The same hand illumiuated'by Roentgen rays 518 

889. Perochirus... 518 

890. Skeleton of perochirus 518 

891. Pcropus 519 

892. Skeleton of peropus 519 

393. Polydactylism 524 

894. Polydactylism in the new-born skeleton 524 

395. Polydactylism and syndactylism of left hand 524 

396. Polydactylism and syndactylism of riglit foot 524 

397. Hermaphrodismus verus lateralis 527 

398. External genitalia of a female pseudohermaphrodite 528 

399. Acardiacus acephalus 532 



LIST OF ILLUSTRATIONS. Xxi 

PAGE 

400. Acardiacus pseudoacormus 532 

401. Pygopagus 533 

403. Ischiopagus 533 

403. Dicephalus dibrachius dipus 534 

404. Diprosopus distomus tetroplithalmus diotus dibrachius 534 

405. Craniopagus parietalis 535 

406. Cephalothoracopagus 535 

407. Thoracopagus tribrachius tripus 536 

408. Polymelos 537 

409. Polymelos 537 

410. Pygopagus parasiticus 537 

411. Thoracopagus parasiticus 537 

413. Thoracopagus parasiticus 538 

413. Epignathus 538 

414. Gelatin plate with colonies of bacteria 554 

415. Streptococcus from a purulent peritoneal exudate 559 

416. Micrococcus-colonics in liver-capillary 559 

417. Cocci grouped in tetrads 559 

418. Sarcina ventriculi " 559 

419. Streptococcus tracheitis in scarlatina 563 

430. Streptococcus pyogenes from phlegmon of stomach 563 

421. Streptococcus erysipelatis in lymph-vessel 563 

433. Section of skin in erysipelas bullosum 563 

433. Erysipelas of head in child of one month 563 

434. Beginning streptococcus phlegmon on trunk 564 . 

435. Streptococcus infection of petrous bone 565 

436. Metastatic haematogenous streptococcus pneumonia 566 

437. Parietal endocarditis of left auricle, due to streptococci , 567 

438. Erythema multiforme caused by streptococci 567 

439. Marked streptococcus infection of kidney 568 

430. Diplococcus pi.eumonise 570 

431. Diplococcus pneumonia in early stage 571 

433. Multiple abscesses of skin caused by staphylococci 573 

433. Miliary abscesses of kidney caused by staphj-lococci 574 

434. Metastatic colonies of staphylococci in liver 575 

435. Gonococci in urethral secretion 577 

436. Urethritis gonorrhoica 577 

437. Bacillus subtilis in different stages of development 581 

438. Clostridium butyricum 581 

439. Anthrax-bacilli in liver capillaries 585 

440. Anthrax-spores , 585 

441. Anthrax pustule 586 

443. Portion of anthrax pustule, containing bacilli 587 

443. Tj'^phoid bacilli from a pure culture 589 

444. Typhoid bacilli with flagella 589 

445. Typhus abdominalis. Section of Peyer's patcli 591 

446. Bacillus pneumonise 595 

447. Nail-shaped stab-culture of pneumonia-bacilli in gelatin 595 

448. Intluenza-bacilli from sputum: 597 

449. Diphtheria bacilli from a pure culture 598 

450. Tetanus bacilli with terminal spores 601 

451. Pest-bacilli 605 

453. Tubercle-bacilli 608 

453. Tissue changes caused by fresh invasion of tubercle-bacilli 609 

454. Giant-cell containing tubercle bacilli 609 

455. Tubercle from a fungoid granulation tissue of bone 609 

456. Tuberculosis of pleura 610 

457. Large-celled tubercle with fibrin 610 

458. Caseous necrosis of tuberculous granulation tissue 611 

459. Miliary tubercle of omentum 611 

460. Fibrocaseous tubercle of lung 613 

461. Fibrous tubercle in thickened synovial membrane 613 

463. Lupus of skin with atypical proliferation of epithelium 617 

463. Tuberculous granulation tissue from tlie synovial membrane of the knee 618 

464. Large solitary tubercle of pia mater cerebelli 618 

465. Tuberculous induration of the lung 619 



xxii LIST OF ILLUSTRATIONS. 

PAGE 

466. Tuberculous induration of the lung 619 

467. Encapsulated caseous focus in lung, with induration 620 

468. Encapsulated caseous focus in lung 620 

469. Tuberculous cavity in tibia 621 

470. Tuberculous ulcer of intestine 622 

471. Beginning pulmonary tuberculosis without catarrh 622 

472. Beginning pulmonary tuberculosis in child of two years 623 

473. Eruption of tubercles in a Ij'mph-gland 624 

474. Tuberculosis of veins in neighborhood of a tuberculous retroperitoneal gland. 625 

475. Haematogenous miliary tuberculosis of liver 626 

476. Tuberculosis of omentum 626 

477. Proliferations of pleura in "pearl-disease" of cattle 628 

478. Initial sclerosis 632 

479. Section of syphilitic initial sclerosis 632 

480. Condyloma latum ani 633 

481. Meningoencephalitis svphilitica gummosa 634 

482. Gumma hepatis 635 

483. Syphilitic ulceration of larynx 636 

484. Congenital syphilitic induration of liver 637 

485. Changes in luiig in congenital syphilis 637 

486. Tissue from a leprous nodule 639 

487. Giant-cell containing lepra-bacilli 639 

488. Section of leprous nodule of skin 640 

489. Leontiasis leprosa 641 

490. Lepra aiuesthetica ulcerosa 642 

491. Lepra aniesthetica mutilans 643 

492. Glanders of cat's testicle 645 

493. Section of rhinoscleroma 648 

494. Hyaline cells and spherules from rhinoscleroma 648 

495. Actinomyces hominis 650 

496. Actinomycosis of the tongue 650 

497. Actinomyces druse surrounded by giant -cells and pus-corpuscles 650 

498. Actinomycosis of lung 651 

499. Frontal section of nose and upper jaw of a cow affected with actinomycosis. . 652 

500. Spirillum rugula and spirillum undula 660 

501. Cholera-spirilla 661 

502. Stab-culture of cholera-spirilla in gelatin 661 

503. Stab-culture of the Finkler-Prior spirillum 665 

504. Spiroclia^te Obermeieri from the blood of a patient suffering with relapsing fever 666 

505. Portion of tissue and isolated cells from a splenic follicle in case of typhus 

recurrens 667 

506. Saccharomyces ellipsoideus 669 

507. Fresh favus-mass consisting of hyplue 669 

508. Thrush, from tongue of man dying of typhoid fever 669 

509. Section through a thrush-covered oesophagus of a small child 670 

510. Mucor corymijjfer in fructification 672 

511. Hyphai of Aspergillus fumigatus, with conidia-bearcrs 672 

512. Culture of Tricophyton tonsurans 677 

513. Amoeba coli mitis 680 

514. Amoeba dysenteriae 681 

515. Balantidium coli 681 

516. Cercomonas intestinalis 682 

517. Trichomonas vaginalis 682 

518. Trichomonas intestinalis 682 

519. Trypanosoma sanguinis murium 683 

520. Section of a bile-duct filled with coccidia 686 

521. Coccidia from the bile-ducts of a rabbit's liver 686 

522. Epithelioma contagiosum 687 

523. Parasites of Epithelioma contagiosum 688 

524. Miescher's sacs from muscle of hog 688 

525. Cj'^cle of development of Coccidium Schubergi 689 

526. Plasmodium malariae of quartan fever 693 

527. Plasmodium malariae of vernal tertian fever 693 

528. Plasmodium vivax of autumnal tertian 694 

529. Anopheles claviger 695 

530. Ookinete of pernicious malaria in intestinal wall of mosquito 695 



LIST OF ILLUSTRATIONS. Xxiii 

PAGE 

531. Oocyst of pernicious malaria, filled with sporozoites 696 

532. Cycle of development of Proteosoma 697 

533. Distoma liepaticum 701 

534. Eggs of Distoma hepaticum 701 

535. Development of the liver-fluke 702 

536. Distoma lanceolatum 702 

537. Distoma spathulatum 703 

538. Distoma Westermanni 703 

539. Distoma haematobium 704 

540. Eggs of Distoma haematobium 704 

541. Head of Taenia solium 706 

542. Half-ripe and ripe segments of Taenia solium , 706 

543. Two proglottides with uterus 706 

544. Segment of Taenia solium, with mature sexual apparatus 707 

545. Eggs of Taenia solium. , 707 

546. Cysticerus cellulosae 707 

547. Cysticerci of Taenia solium 708 

548. Portion of a Taenia saginata 709 

549. Head of Taenia saginata 709 

550. Segment of Ticnia saginata 709 

551. Mature Taenia echinococcus 712 

552. Wall of echinococcus cyst with brood-capsules ' 712 

553. Echinococcus hydatidosus 713 

554. Portion of an Echinococcus multilocularis 714 

555. Bothriocephalus latus 716 

556. Head of Bothriocephalus latus 716 

557. Middle portion of a proglottis of Bothriocephalus latus 717 

558. Eggs of Bothriocephalus latus 717 

559. Free embryo of Bothriocephalus latus 717 

560. Ascaris lumbricoides 719 

561. Egg of Ascaris lumbricoides 719 

562. Oxyuris vermicularis 721 

563. Eggs of Oxyuris vermicularis 721 

564. Male of Anchylostoma duodenale 722 

565. Head of Anchylostoma duodenale. 722 

566. Eggs of Anchylostoma duodenale 722 

567. Anguillula intestinalis 724 

568. Female of Anguillula stercorals 724 

569. Triocephalus dispar 726 

570. Egg of Tricocephalus dispar 726 

571. Sexually mature trichinae 727 

572. Encapsulated muscle -trichinae 728 

573. Filaria or Dracunculus medinensis 729 

574. Embryo of Filaria Bancrofti, known as Filaria sanguinis hominis 729 

575. Female itch-mite 731 

576. Scabies 732 

577. Leptus autumnalis 733 

578. Acarus folliculorum hominis 733 

579. Ixodes ricinus 733 

580. Cephalic end of Pentastoraa denticulatum 733 

581. Male of Dermatophagus communis 734 

582. Male of Dermatocoptes communis 734 

583. Female of Pediculus capitis 735 

584. Male of Pediculus pubis 735 

585. Female of Pediculus vestimentorum 735 

-586. Gastrophilus equi 736 



GENERAL PATHOLOGY. 



INTRODUCTION. 

General Pathology, the science of disease, has for its especial prov- 
ince the investigation, from all sides, of the processes of disease, the deter- 
mination of their nature and significance, their causes and origin, their 
course a7id termination. 

The life of an organism reveals itself by means of certain peculiar 
activities which we regard as the manifestatio7is of life. In the case of 
unicellular organisms these manifestations consist chiefly of changes of 
form, movement, and division of cells, the taking-up of food and the 
giving-off of waste products; the last-named processes being visible un- 
der the microscope in the case of formed material, but in the case of 
soluble substances they are revealed by changes in the chemical compo- 
sition of the medium in which the cells complete itheir existence. In 
multicellular organisms, particularly in the more highly developed 
mammals and in man, these vital functions are much more varied and 
complicated. In the general metabolism of the organism a very great 
variety of tissues and organs takes part : the intestinal tract, the respi- 
ratory apparatus, the blood, and glands of different structure, some 
especial individual function being assigned to each. Eeproduction is 
accomplished by means of special organs and apparatus. Motion is 
dependent upon special tissue formations. The perception of external 
influences is made possible through highly developed sense-organs, and 
the entire organism is controlled by a complicated nervous system, the 
functions of which are so individual and many-sided as to render their 
study extremely difficult. The investigation of the normal processes of 
life, which falls to the province of physiology, is accordingly very diffi- 
cult and complicated, and we are yet far from an exact knowledge of all 
the processes of the healthy or normal life. 

The study of disease-processes, as well as of the normal, takes its 
departure from the life-manifestations of the human body, and such indi- 
viduals are regarded as ill whose functions in part deviate from those recog- 
nized as normal. The science of general pathology, whose exposition 
forms this study, is, accordingly, first of all to be designated as patho= 
logical physiology ; that is, the science which seeks to recognize the 
significance and character of the manifestations of disease. It can, 
however, do justice to this task only when it at the same time deter- 
mines also the anatomical changes which give rise to disturbances of 
function in tissues and organs, the causes which produce them, and their 
mode of origin ; that is, the pathological anatomy, the etiology, and 
the pathogenesis of the processes of disease are essential i)arts of gen- 
eral pathology. 

Every manifestation of life is dependent upon a material substratum, 

1 



2 



INTRODUCTION. 



every form of vital activity presupposes some special condition of this 
substratum, and physiology teaches us that the individual functions of 
tissues and organs are dependent upon the special structure of their in- 
dividual organization. A change of function in this or that direction 
presupposes also a change in the tissue or organ, and experience teaches 
that such changes in reality take place; and, further, that for the same 
a causa efficiens may at times be demonstrated. It is to be noted, however, 
that the tissue-lesion underlying a disturbance of function cannot always 
be discovered, nor is it always possible to ascertain the etiology or patho- 
genesis of the same ; but the number of such cases is constantly dimin- 
ishing through the imj^rovement of our methods of investigation, as 
afforded by means of modern microscopical technique, animal experi- 
mentation, and the utilization of chemical research ; and this number is 
already reduced to a small percentage of pathological processes. The 
experienced physician is, therefore, enabled from given symptoms of 
disease to diagnosticate certain organic changes ; and, further, from the 
same to recognize often the causes of the disease and the manner of its 
origin. 

The symi^tonis of disease may at one time point to a certain organ 
as the seat of disturbance, or at other times the organism as a whole may 
appear to be involved ; we may distinguish accordingly local and gen= 
eral diseases. Not rarely a number of organs may be affected at the 
same time — this may be spoken of as multiple localizations of disease; 
or in other cases the disease may have a localized seat, but runs its course 
with such changes of tissue that a diseased condition of the entire or- 
ganism results. 

The specific grouping of pathological symptoms which repeats itself 
in many cases makes it possible for us to distinguish different forms of 
disease, and occasionally the physician finds it difficult in a given case 
to determine the exact form of the disease. As criteria for the origin of 
different types, the especial causes of the disease, the location of the tis- 
sue-lesion, and the nature of the process are to be considered. There 
results, therefore, a great variety of diseas('-i)ictures; and it is not al- 
ways easy, often impossible, to determine either the seat of the disturb- 
ance, the character of the tissue-lesion, or the causes leading to the same. 

The duration of different diseases is very variable, and we may 
therefore distinguish acute, subacute, and chronic ])ro('(\sses, the last 
extending throngh years or even decades. An illness may tei'ininate in 
recovery and cure or with the death of the affected individual. A cure 
is assumed when all symptoms of disease have vanished, but experience 
teaches that the complete restoration of the affected part often takes 
place iiiuch later than the disappearance of the symptoms. Not infre- 
quently licaliiig is delayed and the disease becomes latent; that is, ex- 
tensive tissue changes remain, the injurious agent is not removed from 
the body, though symptoms of the disease are no longei* present. For 
example, the symptoms of a tuberculous affection may completely disap- 
pear, though foci containing tubercle bacilli are still present in the body 
from which by chance a further extension of the disease may take place, 
and, accompanying this, new symptoms may arise. 

When in the course of a disease a local loss of tissue is not replaced 
by the process of healing, a defect remains ; a defect of large size, on 
the visible external portions of the body, such as the loss of a finger or 
leg, is spoken of as a mutilation. 

If, in the place of a highly organized tissue which has been destroyed, 



INTRODUCTION. 



3 



connective tissue of a lower grade is formed, or if an external defect is 
closed by such formation of tissue, there results a scar. When, as the 
result of some disturbance of the normal intra-uterine development, cer- 
tain tissues at birth present pathological alterations, the condition is 
designated as a congenital malformation or anomaly. If the affected 
organs show functional disturbances, the condition may be termed a con- 
genital disease. 

The broad field covered by general pathology necessitates a narroioing of 
its subject-matter ; and it happens conveniently that a part of pathological 
physiology, which may be designated clinical pathology, is best relegated to 
study at the bedside, to special courses and lectures, or to text-books. The 
disturbances of function pertaining to the different organs and systems, 
heart, nervous system, organs of special sense, respiratory tract, urinary 
apparatus, digestive tract, etc., cannot be discussed in this connection. 

A detailed consideration can be undertaken only of those phenomena of 
disease which are consummated in the elementary constituents of the tissues, 
the tissue-cells and the intercellular substance; and these can be judged and 
properly valued only through an exact study of the anatomical and histological 
changes thereby presented. General pathological anatomy becomes, 
therefore, the indispensable foundation for general pathology ; but it 
leads to a complete knowledge of the processes of disease only when at 
the same time the etiology and pathogenesis of the tissue-lesion are re- 
vealed in a satisfactory manner. 

Literature. 

(Gene) ri I Pa th ology. ) 
American Text-Book of Pathology, Philadelphia, 1901. 

Aschoff unci Gaylord: Cursus der pathologischen Histologie, Wiesbaden, 1900. 
Birch-Hirschfeld : Patholog. Anatomie, 1896-1897; Allgem. Pathologie, Leipzig, 
1892. 

Bollinger : Atlas und Grundriss d. pathol. Anatomie, Miinchen, 1896-1897. 
Bouchard: Traite de pathologie generale, Paris, 1895-1900. 
Coats : Manual of Pathology, London, 1895. 

Cohnheim: Yorlesungen liber allgemeine Pathologie, Berlin, 1882. 
Cornil etRanvier: Manuel d 'histologic pathologique, Paris, 1881. 
Cruveilhier: Anatomie pathologique (Atlas), Paris, 1842. 
Delafield and Prudden : Pathological Anatomy, New York, 1892. 
Diirck: Atlas und Grundriss d. pathol. Histologie, Miinchen, 1900. 
Graupner und Zimmermann : Technik u. Diagnostik am Sektionstisch, Zwickau, 
1898. 

Hallopeau : Traite elementaire de pathologie generale, Paris, 1898. 

Hammarsten : Physiolog. Chemie, Wiesbaden, 1896. 

Henle : Handbuch der rationellen Pathologie, Erlangen, 1846-1853. 

Israel: Praktikum der pathologischen Histologie, Berlin, 1893. 

Karg- und Schmorl: Atlas der pathologischen Gewebelehre, Leipzig, 1893. 

Kaufmann: Specielle patholog. Anatomie, Berlin, 1896. 

Klebs: Die allgemeine Pathologie, i., Jena, 1886, und ii., 1889. 

Krehl : Pathologische Physiologic, Leipzig, 1898. 

Lancereaux: Traite d'anatomie pathologique, i.-iii., Paris, 1877-1889. 

Lazarus-Barlow : A Manual of General Pathology, London, 1899. 

liukjanow: Grundzlige einer allgemeinen Pathologie der Zelle, Leipzig, 1891; 

Grundziige einer allgemeinen Pathologie des Gefasssystems, Leipzig, 1894; 

Grundzlige einer allgemeinen Pathologie der Verdauung, Leipzig, 1899. 
Neumeister: Physiologische Chemie, Jena, 1897. 
V. Noorden: Pathologie des St-offwechsels, Berlin, 1893. 
Orth : Lehrbuch der speciellen pathologischen Anatomie, Berlin, 1893-1897. 
Paschutin : Vorlesungen liber allgemeine Pathologie, St. Petersburg, 1881. 
Perls-Neelsen : Lehrbuch der allgemeinen Pathologie, Stuttgart, 1893. 



4 



INTRODUCTION. 



von Recklinghausen: AUgemeine Patliologie des Kreislaufs u. der Ernahrung, 
Stuttgart, 1883. 

Ribbert: Pathologische Histologie, Bonn, 1896; Die Lehre von dem Wesen der 

Kranklieit in ihrer geschiclitlichen Eutwickelung, Bonn, 1899. 
RindfLeisch : Die Elemente der Pathologic, Leipzig, 1896. 
Rokitansky: Lehrbuch der pathologischen Anatomie, i.-iii., Wien, 1855-1861. 
Rumpel undKast: Patliologisch-anatomiscbe Tafelu, Hamburg. 1892-1897. 
Schmaus : Grundriss der pathologischen Anatomie, Wiesbaden, 1899. 
Strieker: Yorlesungen iiber allgemeine und experimentelle Patliologie, Wien, 1883. 
Tlioma: Lehrbuch der patliolog. Anatomie, Stuttgart, 1894. 
C. Thommasi-Crudeli : Istituzioni di Anatomia Patologica, Torino, 1882. 
Valenti: Lezioni di Patologia Generale, Roma, 1881-1885. 

Virchow: Handb. d. spec. Patholoaie, i.. Erlangen, 1854; Die Cellularpathologie, 
Berlin, 1871. 

"Weicbselbaum : Grundriss der pathologischen Histologie, Wien, 1892. 
Woodliead: Practical Pathology, London, 1892. 



CHAPTER I. 



The Extrinsic and Intrinsic Causes of Disease. 

I. The Origin of Disease through Extrinsic Causes. 

1. Origin of Disease through Deficient Supply of Food and Oxygen, through 
Fatigue, Heat and Cold, Changes of Atmospheric Pressure, and Electrical 
Influences. 

§ 1. From his birth to his death man is coustantly exposed to the in- 
fluences of the world surrounding him, many of these external influences 
being favorable to the normal exercise of his functions, while others are 
unfavorable. 

As long as the human organism is able to offset these influences, 
through independent changes of its relations to the external world or 
through adaptation of its functions to external conditions, it will remain 
in health. If his regulating mechanism no longer sufiices for successful 
opposition to unfavorable external influences, and if he cannot escape 
these or change his conditions of life, man becomes ill or dies. 

For its preservation the body needs first of all a certain amount of 
food, water, and oxygen ; and though it may exist for a short time with- 
out these, an insufficient supply of oxygen, food or water beyond a 
certain limit and after a certain time must of necessity lead to disease 
or death. 

A total deprivation or diminution of the supply of oxygen 4o the 

tissues may take place at any period of life, either because of a lack of 
oxygen in the surrounding medium, or some obstruction to the entrance 
of the oxygen of the air into the lungs or blood, or inability on the part 
of the blood to take up a sufficient amount of oxygen. The foetus in 
utero may be insufficiently supplied with oxygen as a result of diminished 
supply to the mother, premature separation of the placenta, disease of 
the placenta, or compression of the cord, whereby the interchange of 
gases between the maternal and foetal blood is hindered. After birth an 
insufficient supply of oxygen may be due to hindrances to respiration, 
or the child may be so weak that its respiratory movements are insuffi- 
cient to expand the lungs. 

When the supply of oxygen is completely shut off, as may happen 
from the entrance of water or other fluid into the respiratory tract or 
from closure of the air-passages, the affected individual dies in a very 
short time from choking or suffocation. Animals confined in closed 
chambers die as soon as the oxygen of the air reaches two or three per 
cent by volume, the normal volume percentage being 20.8 (CI. Bernard, 
P. Bert). 

If the supply of oxygen is not wholly shut off, but only greatly 
diminished, as in the case of carbon-monoxide poisoning, in which the 
firm combination of carbon monoxide with the haemoglobin prevents the 
taking up of oxygen by the red blood-cells, death by suffocation may 

5 



6 



THE EXTRINSIC CAUSES OF DISEASE. 



take place only after several days. In gradually increasing hindrances 
to the entrance of oxygen and resulting accumulation of carbonic acid 
in the blood, as in cases of narrowing of the Imnen of the larynx through 
inflammatory exudates, compression of the trachea from goitre, weaken- 
ing or obstruction of respiration, etc., a condition of breathlessness, 
cyanosis, convulsions, and disturbances of consciousness is produced, 
which is termed asphyxia. 

If the taking up of oxygen is diminished in only a slight degree but 
for a long time, as in the case of a lessened number of red blood-cells 
^ in oligocythsemia, degenerative processes characterized by increased de- 
struction of albumin and by fatty changes may occur in the tissues and 
organs, and these may lead not only to disease but under certain condi- 
tions to death. 

Total deprivation of food and water leads to a rapid loss of body- 
weight, inasmuch as the fat and albumin continue to be decomposed; 
death finally ensues. According to Lehmann, Miiller, Munk, Senator, 
and Zuntz, the total amount of oxidation in cases of starvation does not 
fall below that of the same individual in the fasting state under the 
same conditions. A marked decomposition of albmnin and loss of water 
take i)lace. In animals death occurs after the loss of about forty per cent 
of the body-weight, about one-half of the loss being due to the waste of 
muscle. 

The fat disappears most rapidly ; even as much as ninety -three per 
cent may be lost. Tlie other organs show diminution of substance in the 
following order: liver, spleen, testicles, muscles, blood, intestines, skin, 
kidneys, and lungs. The heart, nervous system, and bones show the 
least loss of weight ; but, according to the researches of Lehmann, Miiller, 
Munk, Senator, and Zuntz, destruction of bone-tissue takes place during 
starvation, as is shown by the increase of calcium and phosphoric acid 
in the urine, following ingestion of water. In the blood there is a rapid 
diminution of the leucocytes (Luciani) ; the red blood-cells, on the other 
hand, may be relatively increased in number. The organs of animals 
dying from starvation show simple atrophy of the tissue-elements, par- 
ticularly of the liver (Lukjanow), hyperoemia, scattered hemorrhages, 
degenerations, and inflammatory changes, especially in the intestine, 
liver, kidnej^s, and nervous system. 

In the case of total deprivation of food and water, death occurs in 
man after from seven to twelve days; bodily exercise hastens the end, 
ingestion of water may delay it markedly, so that some indi^ iduals have 
been enabled through the use of water to endure a period of total absti- 
nence from food for thirty days or longer, without dying or suffering 
permanent harm. The consumption of water leads to an increased ex- 
cretion of nitrogen in the urine. 

Life may be maintained for a long time upon insufficient nourish- 
ment, but a wasting of the body takes place which may lead to a condi- 
tion of extreme emaciation, marasmus, or cachexia, and finally to death. 
The same thing happens when the composition of the food is unsuitable 
and only a portion of the necessary food-elements is present in sufficient 
amount, so that the body is starved either in albumin, fat, salts, or 
water. Dogs deprived of all nitrogenous food die in from thirty -one 
to thirty-four days (Magendie). When the food is abundant but poor in 
albumin, there occur after a time (in dogs after six weeks) loss of appe- 
tite and repugnance toward the proffered food, with impairment of diges- 
tion and assimilation (Munk). This is especially the case when the food 



DEPRIVATION OF OXYGEN, FOOD, AND WATER. 



r 



is lacking in fat, less so when albumin or the carbohydrates are wanting. 
It is very probable that the lessened absorption is chiefly due to diminished 
secretion of the digestive juices, this being capable of quantitative de- 
monstration in the case of the bile. The fseces are finally nearly desti- 
tute of bile. 

An insufficient supply of iron for a long period gives rise to anaemia 
and general disturbances of nutrition. 

If for experimental purposes an animal well supplied with food is to= 
tally deprived of water, there is a rapid loss of body-weight followed 
in from eight to twelve days by death. The pathological changes found 
in the different organs are similar to those resulting from starvation. 
They are caused partly by lack of water and insufficient absorption of 
food, and partly by the retention of harmful products of metabolism. 

Literature. 

(Eesnlts of Bimimslied ^upphj of Oxygen, Food, and Water.) 

Ahlfeld: Der Cebergang der intrauterineu Athmung zur extrauterinen, 3Iarburg, 
1891. 

Beneke: Grundlinien der Pathologie des Stoffwechsels, Berlin, 1874. 
Bischoff uud Volt: Die Gesetze der Ernahrung des Fleischfressers, 1860. 
Coen: Sull' inanizione acuta. Bull, delle Scienze Med. di Bologna, ser. vii., vol. i., 
1S90. 

Daddi et Treves : Observations sur I'asphyxie lente. A. ital.'de biol., xxviii., 1897. 

Dennig: Bedeutung der Wasserzufuhr flir den Stoffwechsel. Zeit. f. Tber., i., 1898. 

Dreyfus-Brissac : De I'asphj^xie non toxique, Paris, 1883. 

Ehrlich : Das Sauerstoffbedurfniss des Orgauismus, Berlin, 1885, 

Frankel: Einfluss d. verminderten Sauerstoffzufuhr. Vircb. Arcb., 67 Bd., 1870. 

Halliburton: Lebrb. der cbemiscben Piiysiologie und Patbologie, Heidelberg, 1896. 

Hofmann: Lelirbucb der gericbtl. Medicin, Wien, 1895. 

Hoppe-Seyler : Stoffwecbsel bei Sauerstoffmangel. Festschr. d. Assist, f. Vircliow, 
Berlin, 1891. 

Krehl : Die Atbmung. Patbol. Pbysiologie, Leipzig, 1898. 

Lehman, Miiller, Munk, Senator, unci Zuntz : Untersucbung an zwei bungernden 

Menscbcn. Yircb. Arcb., 131 Bd., Supplement, 1893. 
Luciani: Das Huugern (libersetzt von O. Frankel), Leipzig, 1890. 
Lukjanow: Verand. d. Zellkerne unt. d. Einfl. d. Hungerns. Arcb. des Sc. biol., vi. 

uud vii., 1897 u. 1898. 
Meltzer and Norris : On the Influence of Fasting upon tbe Bactericidal Action of 

the Blood. Jour, of Exp. Medicine, 1899. 
Monti: Alterat. del sist. nervoso nell' inanizione. Arcb. ital. de Biol., xxiv., 1895. 
Miiller: Stoffwecbseluntersucbungen bei Krebskranken. Zeitscbr. f. klin. Med., xvi., 

1889. 

Muhlmann : Russiscbe Literatur liber die Patbologie des Hungerns (zablreicbe und 
vielseitige Untersucbungen). Centralbl. f. allg. Pathol., x., 1899. 

Munk: Ueber die Folgen eiuer ausreicheuden aber eiweissarmen Nabrung. Yirch. 
Arch., 132 Bd., 1893. 

V. Noorden: Pathologie des Stoffwecbsels, Berlin, 1893. 

Ottolenghi: Osserv. sperim. sul sangue asfittico. Arch. p. le Sc. Med., xvii., 1893. 
Peri: Alterations du S3"st. nerv. prod, par I'inanition. Arch. ital. de Biol., xviii., 1892. 
Pernice und Scagliosi: Wirkung d. Wasserentziehung. Yircb. Arcb., 139 Bd., 1895 
(Lit.). 

Penzoldt u. Fleischer: Einfluss von Respirationsstorungen. Yircb. Arch., 87 Bd., 
1882. 

Runge : Die Krankheiten der ersten Lebenstage, Stuttgart, 1893. 

Statkewitsch : Yeriinderungen d. Muskeln u. Driiseu b. Hungern. Archiv f . exp. 
Path., 33 Bd., 1894. 

§ 2, An unusual demand upou the functional activity of an organ 
for an extended period of time leads sooner or later to a state of ex= 
haustion, whicli is, in part, due to the consumption of cell -substance, 



8 



THE EXTRINSIC CAUSES OF DISEASE. 



and in part to the formation of toxic products of metabolism, whereby 
the organ is incapacitated for further extended activity. Most often 
the results of overwork are manifested in the muscles and nervous 
system in the form of such symptoms as soreness and stiffness of the 
muscles, mental excitement, sleeplessness, heavy feeling in the head, loss 
of appetite, great Tveakness, unnatural sweating, and sometimes fever. 
Overwork of the heart leading to exhaustion may cause death. This may 
occur either when the heart is for a short time taxed to the extreme limit 
of its power or when for a longer period it works slightly under its 
maximum capacity. If the exhausted tissues are permitted to rest and 
supplied with an abundance of nourishment, the loss of cell -material 
due to the excessive activity will be replaced, the products of metabol- 
ism, which are hindering the functional activity of the tissue, will be 
removed, and the part restored to its normal condition. 

If a tissue is frequently subjected to excessive functional demands, 
and if the periods of rest are too short to admit of its complete restora- 
tion, there will result ultimately a condition of permanent functional in- 
sufficiency, a chronic exhaustion, which may under certain circumstances 
manifest itself in a degeneration or atrophy of the affected organ. For 
example, a muscle through overwork may become atrophic, and a brain 
too constantly stimulated to activity without proper periods of rest may 
finally reach such a state of weakness and exhaustion that it is incapable 
of i:)erformiug even its normal function. Through rest and properly 
regulated nourishment such a brain may recover ; but beyond a certain 
limit of exhaustion the functional insufficiency may become permanent 
and eventually manifest itself in anatomical changes. 

A very severe over-stimulation of tlie nervous system, even for a 
very short time, may under certain conditions lead to a paralysis of its 
functions, which, in case the heart and respiratory apparatus are af- 
fected, may cause death, but in the majority of cases is of a transitory 
nature. 

Overwork of any organ is more cpiickly followed by fatigue and 
functional insufficiency in the case of impaired nutrition. Fatigue and 
insufficiency of the heart are most frequently observed when the general 
nutrition is lowered, as in cases of fever, or when there is deficient oxy- 
genation of the blood, as in poorly compensated heart lesions or pulmo- 
nary diseases. 

It is very probable that overwork lowers the resistance of the body 
to various infections. 

"SATien the functional demands upon a muscle or gland are only mod- 
erately increased, and if the nutrition is good and in proportion to the 
increase of labor, the affected tissue becomes hypertrophied, and is 
thereby enabled to i)erform the increased work permanently. 

Literature. 

(Overexertion and Fatigue.) 

Abelous: Contrib. a I'etiide de la fatigue. Arch, de Pliys., v., 1893. 

Blake and Larrabee : Observations upon Long-Distance Runners. Boston Med. and 

Surg. Jour., 1903. 
Bouveret: La neurasthenie, Paris, 1891. 
Brauns: Die Neurasthenie, Wiesbaden, 1891. 

Carrieu: De la fatigue et de son influence pathogenique, Paris. 1878. 

Edinger: Neue Theorie liber die Ursachen einiger Nervenkrankheiten, Leipzig, 1894. 



THE EFFECTS OF HIGH TEMPERATURE. 



9 



E:b: Die zunelimende Nervositat unserer Zeit, Heidelberg, 1893. 
De Fleury: Pathogenie de repuisement nerveux. Rev. de Med., 1896. 
Guerrini: Action de la fatigue sur les cellules nerveuses. Arch. ital. de Biol.: xxxii., 
1899. 

Kraepelin: Zur Ueberburdungsfrage, Jena, 1897 (Lit.). 

V. Krafft-Ebing : Lehrbuch der Psychiatric, 1898 ; Gesunde u. kranke Nerven, 1895. 
Krehl u. Romberg; Bedeutung d. Herzmuskels u. d. Herzganglion. f. d. Herzthatig- 

keit. Arch. f. exp. x'ath., 30 Bd., 1892. 
Leyden: Herzkrankheiten in Folge v. Ueberanstrengung. Zeitschr. f. klin. Med., 

xi., 1886. 

Marfan: Fatigue et surmenage. Path. gen. publ. par Bouchard, i., 1895. 
Mosso : Die Ermlidung, Leipzig, 1893. 

Seitz: Ueberanstrengung d. Herzens. D. Arch. f. klin. Med., xi., 1873, u. xiii., 1874 
(Lit.). 

Williams and Arnold: The Effects of Violent and Prolonged Exercise upon the 

Heart. Phil. Med. Jour., 1899. 
Ziehen: Neurasthenic. Eulenburg's Realencyklop., xvii., 1898 (Lit.). 

§ 3. High temperatures may act, either through local destruction oj 
tissue (hiorning) or through overheating of the entire body. The latter 
condition is possible only when the body is exposed to an increased tem- 
perature for such a time that it cannot protect itself from overheating 
by increased heat- dispersion. In dry air of from 55-60° C. (131-140° 
F. ) the most profuse perspiration is no longer able to protect the body 
permanently from overheating, and in a moist atmosphere the same is 
true at even lower temperatures. 

If rabbits are placed in well-ventilated incubators at a temperature 
of 36-40° C. (96.5-104° F.), their body temperature will rise to 39-40° 
C. (102.3-104° F. ), the respiration and pulse being at the same time 
greatly increased in frequency. A very marked elevation of body tem- 
perature may lead in one to three days to death through paralysis of the 
nervous and muscular systems, the chief symptoms being a marked in- 
crease of both respiration and heart's action. If the increase of body tem- 
perature is not greater than 2-3° C. (3-5° F. ), the animals may, if 
properly nourished, live from ten to thirty days or even longer, but they 
will lose in weight and ultimately die, showing before death a gradually 
increasing diminution of haemoglobin and of red blood-cells. Degenera- 
tive changes, particularly fatty degeneration, occur in the liver, kidneys, 
and heart-muscle. During the experiment there is an increased produc- 
tion of urea. 

If the human body is subjected to high temperatures, it may become 
overheated, and the condition known as heat=stroke may result. The 
pulse-rate is increased, the respiration very rapid and labored, the pupils 
are dilated, and finally death may occur as in the case of the animals 
made the subject of experiment. The occurrence of heat-stroke is 
favored by heavy bodily labor, interference with heat-dispersion through 
impermeable clothing, or by a lack of water in the body. 

The direct action of the rays of the sun upon the head may cause 
cerebral and meningeal irritation, a condition characterized by hy- 
persemia and inflammatory exudations, and known as sun=stroke or 
insolation. 

The local effects of heat upon the skin, burns, are, according to the 
intensity of the heat and the time of its duration, either hypersemia 
(burn of first degree), formation of a blister (second degree), tissue- 
eschar (third degree), or carbonization (fourth degree). The heat pro- 
duces local changes in the tissues, and kills them at a certain height of 
temperature or after a certain time of exposure to its action. 



10 



THE EXTRINSIC 



CAUSES 



OF DISEASE. 



Wlien a large part of the surface of the body, about one -third, is 
burned, the atfected individual usually dies, even though the burn is 
only of a slight degree and eschars are not formed. This phenomenon 
has been explained in various ways. Billroth, Foa, Mendel, and others 
believed the cause of death to lie in a suppression of perspiration and 
the resulting accumulation of toxic substances in the blood ; while oth- 
ers, as Sonnenburg and Falk, sought the cause in a reflex lowering of 
vascular tone. In the foudroyant cases, according to Sonnenburg, the 
overheating of the blood causes paralysis of the heart. Ponfick, Klebs, 
von Lesser, and others, on the other hand, are of the opinion that the 
fatal issue is due to injury and destruction of the red blood -cells. Sil- 
bermann, Welti, and Salvioli also seek the cause of death in an injury to 
the blood, emphasizing, however, not so much the destruction of the red 
cells as the occurrence of stasis and coagulation of the blood in the 
vessels of different organs, which are interpreted as resulting from the 
changes in the blood. On the other hand, Kijanitzin and Parascandolo 
hold that there is formed in the bodies of burned individuals a poison 
(ptomain) which has an injurious effect upon the nervous system. 

The anatomical findings in fatal cases of superficial burns would in- 
dicate, when death has not resulted very quickly from the severe shock 
to the nervous system and the overheating of the body, that the cause 
of death is to be sought in the changes in the blood and in disturbances 
of the circulation. The blood-changes consist in destruction of the red 
blood-cells, or in such injury to them as to diminish their function and 
to give rise at the same time to a deposit of the products of destruction 
and of haemoglobin in the liver, spleen, and kidneys. The changes are 
further characterized by a tendency on the part of the blood to stasis 
and intravascular coagulation, through which vessels of both the pul- 
monary and the systemic circulation may be obstructed. In this con- 
nection should be mentioned also the fact that both during life and after 
death venous stasis and luTmorrhages, as well as arterial antemia, are oc- 
casionally observed, and that local tissue -degenerations and necrosis may 
occur in certain organs, as, for example, in the kidneys, liver, mucosa 
V of the stomach and intestine, bones, and soft parts. 

Low temperatures act in the same manner as high ones, in part 
throngh local injury and death of tissues, in part through refrigeration 
of the entire body. Severe and lasting lowering of temperature causes 
tissue death ; after mild chilling there occur, as the result of tissue-de- 
generation, thrombosis, hj pertemia, and exudations which are relatively 
rich in leucocytes. A very short refrigeration at the freezing-point is 
sufficient to produce degenerative changes which are quickly followed by 
regenerative proliferation on the part of the cells remaining uninjured. 
Epithelial thickenings may be produced (Fuerst) by repeated slight re- 
frigerations (as well as by repeated slight increase of temperature). 
The tips of the extremities, nose, and ears are the most easily frozen. 
After repeated chillings of mild degree inflammatory redness and swell- 
ing of the skin, associated with severe itching, often occur {chilbJaius, 
perniones). 

If the temperature of the entire body be markedly lowered, a condi- 
tion of general paralysis results from the diminished excitability of the 
tissues, the nervous system and heart being especially affected. The 
sensorium becomes dulled, the heart-beat and respiration gradually grow 
weaker, and finally cease entirely. If the body be again warmed, be- 
fore the excitability of the tissues is wholly lost, the power of movement 



THE EFFECTS OF HIGH AND LOW TEMPERATURES. 



11 



in the limbs is gradually restored, aud after a time consciousness re- 
turns. In man, instances of complete recovery have been observed, even 
after refrigeration of the body to from 24-30° C. (75-86° F.). 

Besides the more severe forms of local or general lowering of the tis- 
sue temperature there may occur, as harmful pathogenic influences, mild 
general or local chillings, the so-called colds, as the result of which dis- 
ease-phenomena may manifest themselves partly at the seat of chilling, 
partly in organs in distant parts of the body. For example, after wide- 
spread refrigeration of the skin there may occur diarrhoea, catarrh of the 
respiratory tract, or disease of the kidneys; after local chilling of the 
skin, painful affections of the deep-seated muscles. The exact relation 
between these phenomena and the refrigeration is unknown (the oft-re- 
peated hypothesis that they are due to hyperaemia of the internal organs 
caused by the chilling of the body-surface has not been proved), but 
there is no reason on this account to deny the existence of diseases caused 
by cold. Though many diseases formerly attributed to "catching cold" 
have been shown to be of infectious origin, there yet remain a number 
of diseased conditions for which we know no other etiology than that of 
refrigeration. Conditions of the body in which the skin is hypersemic 
and the perspiratory function active favor the taking of cold. Many in- 
dividuals appear to possess a predisposition on the part of certain tissues 
to the effects of refrigeration ; in one person certain muscles, in another 
the mucous membranes will be affected. 

According to the view of many writers, refrigeration of the body 
increases the susceptibility to infection, so that, for example, the patho- 
genic bacteria which may be present in those cavities of the body acces- 
sible from without may, after such refrigeration, be able to exert their 
injurious influences upon the tissues. 

According to Pfliiger and others, all the vital processes may be brought to a stand- 
still through refrigeration, without its being impossible for a recovery to take place 
from the apparent death. This may happen even when the animal is frozen to a solid 
mass. Preyer also holds the opinion that the continuit}' of life may be wholly inter- 
rupted by refrigeration, and designates subjects who are thus "lifeless," but still capa- 
ble of living, as anahiotic. Frogs are said to remain capable of life for many hours 
even though the temperature be reduced to —2.5° C, at which temperature the heart 
is frozen. According to the investigations of Koch, such anabiosis of solidly frozen 
animals is possible when only a portion of the water contained in the body of the ani- 
mal is frozen and when the thawing process takes place slowly. In the case of rapid 
thawing strong diffusion currents are set up between the water coming from the ice- 
crystals and the concentrated albuminous solutions of the blood and the tissues; and 
these currents may exert a damaging effect upon the latter. 

According to the investigations of J. Dewar {Proc. of the Royal Sac, London, 1900), 
the seeds of v/heat, barley, mustard, peas, and pumpkins do not lose their germina- 
tive power when put into liquid hydrogen; that is, in a temperature of —250°. 
Further, the protoplasm under these conditions was not changed by the cold. 

Literature. 

{Effects of High and Loio Temperatures.) 

Alonzo: xllteraz. delle fibre nervose in sesc. al congelamento. A. p. le Sc. Med., xiii., 
1889. 

Ansiaux: La mort par le refroidissement, Bruxelles, 1889. 

Bardeen: A Review of the Patholog}^ of Superficial Burns, Johns Hopkins Hosp. 
Rep., vol. vii. 

Dittrich: Ueber Hitzschlag. Zeitschr. f. Heilk., xiv., 1893 (Lit.). 
Fraenkel: Befunde bei acut. Todesf alien nach Hautverbrennung. Deut. med. 
Wochenschr., 1889. 



12 



THE EXTRINSIC CAUSES OF DISEASE. 



Fuerst: Venind. d. Epidermis durch leichte Warme- und Kiilteeiriwirkung. Beit. v. 
Ziegler, xxiv., 1898. 

Gottstein: Klimatische Einfltisse als Krankheitsursache. Ergebn. d. allg. Path., iv., 
Wiesbaden, 1899. 

Grawitz: AViderstandsfahigkeit lebender Gewebe. Deut. med. Wocbenschr., 1897. 
Heidenhain, B. : Inspiration erwarmter feuchter Luft. Vircli. Arch., 70 Bd., 1877. 
Hochhaus: Gewebsverand. nach Kalteeinwirkung. Yirch. Archiv, 154 Bd., 1898. 
Horvath.: Abkiihlungsversuche. Cent. f. d. med. Wiss., 1873; Arch. f. d. ges. Phys., 
xii., 1875. 

Jacubasch: Sonnenstich u. Hitzschlag, Wien, 1881. 
Keferstein: Der Erfrierungstod, Berlin, 1893. 

Kisskalt: Disposition, Erkaltimg u. Abhartung. Mtinch. med. Wochenschr., 1900. 
Koch.s: Wirkung der Kalte imd Anabiose. Biol. Cent., 1890, u. xv., 1895. 
Kijanitzin: Ursache des Todes nach Hautverbrennung. Yirch. Arch., 131 Bd., 1893. 
Koster: Hitzschlag. Berl. klin. AVochenschr., 1875. 

Krieg-e: Hyaline Yeranderuneen der Haiit durch Erfrierungen. Yirch. Arch., 116 
Bd., 1889. 

Laloy : Scheintod u. Wiederbelebimg als Anpassung an Kalte. Biol. Cbl., xx., 1900. 
Lefevre: Reactions consec. aiix refrigerations. Journ. de phys., ii., 1900. 
LeNoir: Agents physiques. Pathol, gen. publ. par Bouchard, i., 1895. 
Lesser: Ueber die Todesursachen nach Yerbrennungen. Yirch. Arch., 79 Bd., 1830. 
MaseiLold: Sonnenstich u. Hitzschlag. Eulenburg's Realencyklopadie, xxii., 1899. 
Markusfeld u. Steinhaus: Todesursache nach Yerbriihung. Cent. f. allg. Path., vi., 
1895. 

Naunyn: Kritisches u. Experimentelles z. Lehre v. Fieber. Arch. f. exp. Path., 

xviii., 1884. 
Obemier: Der Hitzschlag, Bonn, 1889. 

Parascandolo : Alterat. du S3'st. nerveux dans les brUlures. Arch, de phys., x., 1898 
Pfliig-er: Die allgemeinen Lebenserscheinungen, Bonn, 1889. 

Ponfick: Todesfalle nach Hautverbrennungen. Berl. klin. Woch., 1876, 1877, u. 1883. 
Pictet: L'Emploi des basses temper. Jahresber. uber 1893 v. Hermann, ii., 1895. 
Preyer: Ueber Anabiose. Biol. Centralbl., xi., 1891. 

Rischpler: Histol. Yeranderungen nach der Erfrierung. Beitr. v. Ziegler, xxviii., 
1900. 

RubemarLrL : 1st Erkaltung eine Erkrankungsursache? Leipzig, 1898. 
Salvioli: Causa della morte per scoltatura. Yirch. Arch., 125'Bd., 1891, u. Arch. ital. 
de Biol., XV., 1891. 

Silbermann : Ursachen d. Todes nach Hautverbrennungen. Yirch. Arch., 119 Bd., 
1890. 

Sonnenburg: Yerbrennungen. Deutsch. Chirurgie, Lief. 14, Stuttgart, 1879. 
TJschinsky: Wirkung der Kalte auf verschiedene Gewebe. Beitr. v. Ziea'ler, xii., 
1892. 

"Werliovski: Wirkung erhohter Eigemvarme. Beitr. v. Ziegler, xviii., 1895 (Lit.). 
Weg-ner: Abkiihlung blossgelegter Organe. v. Langenbeck's Arch., xx., 1876. 
Welti: Todesursache nach Hautverbrennungen. Beit. v. Ziegler, iv., 1889; Cent f 
allg. Path., 1890. 

Zieg-ler: Wirkung erhohter EigenwMrme. Yerh. d. Congr. f. inn. Med., 1895. 

§ 4. A sudden lowering of atmospheric pressure, as in the case of 
mountain -climbing and baUoon ascents, may cause conditions of great 
exhaustion, with marked palpitation of the heart, unconsciousness, ir- 
regular breathing, and sometimes vomiting, and bleeding from the gums 
and lips. These sj^mptoms depend most probably upon a lacl: of oxygen 
(P. Bert), the capillaries of the lung being unable to take up suflacient 
oxygen from the highly rarefied air. According to the investigations of 
Schumburg and Zuntz, it appears that a given amount of labor calls for 
a greater amount of oxygen at an increased elevation than at a lower 
level. The symptoms of mountain-sickness appear at a lower elevation 
than those of balloon-sickness, owing to the demands made upon the 
muscles in the former case during the climbing. During the building of 
the Gorner Grat Eail way it was "found that at a height of 2,700-3,000 
metres the capacity of the laborers was diminished to a third. The oc- 
currence of haemorrhages is probably due to the formation of fissures in 



CHANGES OF ATMOSPHERIC PRESSURE: ELECTRICITY. 



13 



the mucous membraues, caused by drying due to the rapid evaporation 
(Hoppe-Seyler, von Eecklinghausen). 

According to the researches of Egger, Miescher, and others, a sojourn 
in high altitudes leads, after a short time, to an increase in the number 
of red cells and a greater haemoglobin -content of the blood. 

Schauniann and Eosenquist hold that the same phenomenon may be 
observed in animals confined for some time in bell -jars at a lower atmos- 
pheric pressure. Other authors (Schumburg, Zuntz, Gottstein) oppose 
this view, and maintain that the phenomenon is due either to a thicken- 
ing of the blood from loss of water and to changes in the distribution of 
the blood, or to changes in volume of the measuring-apparatus; they 
endeavor to explain the favorable effects which many individuals expe- 
rience from a residence at high altitudes by certain stimulating influ- 
ences (greater exposure to sun's rays) which affect the nervous system 
and cause increased metabolism. According to Marti, intense and ;pro- 
longed irradiation of the body stimulates the formation of red blood-cells 
and to a lesser degree also that of the hsemoglobin. 

A sojourn in diving-bells or caissons, such as are employed in build- 
ing operations beneath the water, in which the atmospheric pressure is 
increased, under certain conditions, as high as four atmospheres or even 
greater, causes a slight difficulty in breathing and a relatively unimpor- 
tant increase of the pulse -rate. If a change be made quickly from the 
compressed atmosphere to air of ordinary pressure, there may occur 
within an hour a condition of great fatigue, tightness of the chest, ring- 
ing of the ears, cramps in the muscles, pains in the joints and limbs, 
haemorrhages from the nose, ears, and lungs, dilatation of the pupils, and 
under certain conditions paralysis, coma, delirium, and even death after 
an interval of from one to twenty days. The cause of these phenomena 
is probably to be found in the sudden escape from the blood of nitrogen 
which had been absorbed under the high pressure (von Leyden), or in an 
obstruction of the blood-vessels of the spinal cord through the formation 
of gas-bubbles (Hoche). According to experimental investigations of 
Heller, Mager, and von Schrotter, the blood, after rapid removal of 
pressure, contains free gas (almost exclusively nitrogen), so that free gas 
circulates in the blood. The researches of von Leyden and von Mki- 
foroff show that in fatal cases associated with paralysis areas of de- 
generation are found in the white columns of the spinal cord, in which 
individual nerve-fibres are torn apart, presenting marked changes in the 
form of swelling of the axis-cylinders, disintegration of the medullary 
sheaths, and the formation of vacuoles in the place of the nerve-fibres. 
These disturbances are regarded as due to the production of gas-bubbles 
within the spinal cord. If the gray matter is involved, the ganglion - 
cells may also degenerate. 

Changes in the electrical condition of the atmosphere and in the 
magnetic state of the earth produce no demonstrable changes in the hu- 
man body; on the other hand, electric discharges, as lightning-stroke, 
may cause, in part, local burns (Fig. 1), and, in part, lesions of the 
whole body. Under certain circumstances lightning -stroke causes lacer- 
ation of internal organs, as, for example, of the heart and liver. The 
most frequent and important effect of lightning -stroke is a paralysis of 
the nervous system, which gives rise to a severe dyspnoea, which may 
be fatal after a few minutes or hours or which may gradually pass away 
after several hours, days, or weeks. Only rarely do individual nerve- 
trunks remain permanently paralyzed. A transitory paralysis may oc- 



14 



THE EXTRINSIC CAUSES OF DISEASE. 




cnr when the electrical discharge has not passed through the body but 
has descended in its neighborhood. 

In individuals who have been struck by lightning there may be found 
slight or severe burns of the skin corresponding to the points of entrance 
and exit of the current, and various injuries to the tissues in the course 
of its path through the body. The marks of the burn are for the greater 

part red, and form peculiar branching 
zigzag lines, the so-called lightning fig- 
ures (Fig. 1), which are essentially a hy- 
persemia, and soon disappear if the burns 
are not severe. 

The passage of powerful electric 
currents of high tension, such as are 
generated by dynamos, through the hu- 
man body, as may happen when an in- 
dividual is placed in a circuit or comes 
into contact with an uninsulated con- 
ductor, may give rise to severe disturb- 
ances or cause death. According to 
Kratter, the lower limit of danger occurs 
at a tension of about five hundred volts. 
Alternating currents are much more 
dangerous than continuous ones of the 
same strength and tension. When the 
eifects are not fatal, the injured person 
is suddenly rendered unconscious, this 
condition lasting for a few minutes or 
several hours, and for several days aftei'- 
ward symptoms of vertigo, prostration, 
headache, and palpitation of the heart 
may persist (Kratter). At the points of contact more or less severe 
burns are produced. 

In fatal cases, death takes place suddenly or rarely after ten or thirty 
minutes. The autopsy findings, aside from the burns at the points of con- 
tact, are evidences of suffocation and hypervenosity of the blood, stasis 
of the blood within the thoracic vessels, and often small scattered 
haemorrhages which are due partly to suffocation, and partly to the 
direct action of the current. The cause of death is paralysis of the cen- 
tre governing the resi)iration or the heart's action. 



Fig. 1.— Lightning-figures on the shoul- 
der, breast and arm of a woman struck by 
lightning. 



Literature. 



{Effects of Changes of Atmospheric Pressure and of Polarization.) 
Bert, P. : La pression barometrique, Paris, 1878. 

Egger: Veranderungen d. Blutes im Hochgebirge. Congr. f. inn. Med., Wiesbaden, 

1893; u. Arch. f. exp. Path., 39 Bd., 1897. 
Gottstein: Klimat. Einfliisse als Krankheitsursachen. Ergebn. d. allg. Path., iv., 

Wiesbaden, 1899; Yermehrung der rothen Blutkorp. im Hochgebirge. Munch. 

med. Woch., 1899. 

Heller, Mager, Schrotter: Mitth. iibcr Caissonarbeiter. Klin. Woch., 1895; Unter- 
SLich. liber d. Wirkimg rascher Veranderungen d. Luftdruckes. Pfliiger's Arch., 
67 Bd., 1897; Luftdruckerkrankungen, Wien, 1900. 

Hirsch: Handbuch der histor.-geogr. Pathologic, Stuttgart, 1882-1883. 

Hoche: Luftdruckerkrankung d. Centralnervensystems. Berl. klin. Wochenschr., 
1897. 



MECHANICAL INFLUENCES. 



15 



Hoppe-Seyler: Miiller's Arch., 1857; unci Physiol. Chemie, Berlin, 1877. 
Jourdanet: L'Influence de la pression de I'air, 1875. 

Leyden: Durch plotzl. Verminderung d. Barometerdrucks entsteh. Riickenmarksaffec- 
tion. Arch. f. Psych., ix., 1879. 

Loewy u. Zunz: Einfluss d. verdiinnt. Luft. Pflliger's Arch., 1897. 

Marti: Wirkung der Hautreize und Belichtung. Verh. d. Congr. f. inn. Med., Wies- 
baden, 1897. 

Mercier: L'Influence de I'altitude. Arch, de phj^s., vi., 1894. 

Miescher: Bezieh. zwisch. Meereshohe u. Beschaftenh. d. Blutes. Corrbl. f. schweiz. 
Aerzte, 1893. 

Mosso: Der Mensch auf den Hochalpen, Leipzig, 1899. 

Nikiforoif: Veranderungen d. Kuckenmarks in Folge schneller Herabsetzung des 

barometrischen Druckes. Beitr. v. Ziegler, xii., 1892. 
Sch.aumann u. Rosenqvist: Blutverand. im Hohenklima. Zeit. f. klin. Med., 35 

Bd., 1898. 

Schumburg- und Zunz : Einwirkung des Hochgebirges. Pfliiger's Arch., 63 Bd., 1896. 
Snell: Compressed-Air Illness, London, 1896. ' 
Wolff: Einfluss des Gebirgsklimas auf d. Menschen, Wiesbaden, 1895. 
Zunz: Pathogenese der durch Luftdrucksanderungen erz. Krankheiten. Fortschr. d. 
Med., XV., 1897. 

{Effects of Lightning and of Electrical Currents.) 

D'Arsonval: L'energie electrique. Path. gen. publ. par Bouchard, i., Paris, 1895. 

Dillner: Ueber die Wirkung des Blitzes. In. -Diss., Leipzig, 1865. 

Ebertz: Ueber Blitzverletzungen. In. -Diss., Tubingen, 1892. 

Haberda: Tod tung durch Blitzschlag. Wiener klin. Wochenschr., 1891. 

Kratter: Wirkung d. Blitzes. Vierteljahrsschr. f. ger. Med., 1891; Tod durch Elek- 

tricitat, AVien, 1896 (Lit.); Elektrische Verungliickungen. Eulenb. Jahrb., vi., 1896 

(Lit.). 

Liman: Blitzschlag. Deutsch. med. Wochenschr., 1885. 

Mills and Weisenburg" : The Effects on the Nervous System of Electric Currents of 

High Potential. Univ. of Penn. Med. Bull., 1903. 
Oesterlen: Blitzschlag. Maschka's Handb. d. ger. Med., i. 

Prevost et Battelli: La mort par les decharges electriques. J. de phys., i., 1899. 
Vincent: Contrib. a I'hist. medicale de la foudre, Paris, 1875. 

2. The Origin of Disease through Mechanical Influences. 

§ 5. Traumatic influences of various I<:inds leading to concussion, 
bruising, and laceration of tissue are of very frequent occurrence, and 
act partly through the tearing and destruction of tissue, partly through 
changes in tissue-organization not recognizable to the naked eje, and 
partly through lesions and ruptures of the blood- and lymph -vessels, and 
through irritation and paralysis of nerves. The sequelae are partly 
necrosis and destruction of tissue, partly disturhances of circidatio7i, inflam- 
matioyi, and regenerative proliferations. Frequently repeated mechanical 
traumatisms of slight degree, such as rubbing, may give rise to congestive 
hypercemia and inflammations, which may lead further to hyperplastic 
growths of tissue. If large quantities of insoluble dust particles are con- 
tinuously taken into the lungs, extensive changes may occur in these or- 
gans and, under certain circumstances, in other organs. As a result of 
prolonged pressure and diminution of space, atrophy of an organ or tissue 
may occur (corset-liver). 

After a single or after frequently repeated trauma, there may de- 
velop under certain conditions at present unknown to us, malignant new- 
formations of tissue called tumors. Trauma may further pave the way 
for an infection, either in that the wound caused by the trauma is in- 
fected at the time of injury or is secondarily infected from without ; or that 
micro-organisms were previously present in the body under conditions in- 
hibiting their growth, and these find in the injured tissues a suitable soil for 
growth, so that to the trauma an infection is joined. 



16 



THE EXTRINSIC CAUSES OF DISEASE. 



Traumatic influences affect, first of all, the external parts of the 
body ; but it may happen, either with or without visible injury to ex- 
ternal parts, that internal organs may be injured, and the internal 
lacerations, necroses, and haemorrhages thus produced may be followed, 
not only by inflammations and reparative tissue proliferations, but also 
by malignant neoplasms (as, for example, after fractures of bones), and 
by infective processes. 

Mechanical lesions (also thermal, electrical, and corrosive) run a spe- 
cial course, if through the local injury the nervous system becomes in- 
volved. Such involvement occurs either through the direct action of 
the trauma upon the central nervous system ; or, by the stimulation of 
the sensory or sympathetic nerves, the central nervous system may be 
so affected that a number of additional nervous symptoms follow. 

If the direct concussion of the cranium is followed by paralysis of 
the cerebral function and unconsciousness, the condition is termed 
commotio cerebri or cerebral concussion. This term is especially used 
when the trauma has produced no visible changes in the structure of the 
brain, or at least none of any size or importance. 

Excessive stimulation of the peripheral nerves may cause a reflex in- 
hibition or paralysis, involving chiefly the functions of the heart and 
respiratory apparatus ; the symptoms thus produced being collectively 
designated as shock. The most frequent causes of shock are injuries to 
the spinal column, abdominal cavity, and scrotum, less frequently to 
the extremities and thorax. Further, shock may be caused by light- 
ning-stroke, burns, corrosions of the skin, fear, and psychical emotions 
through whatever avenue of perception they may be called forth. In- 
dividuals whose nervous systems are in a certain condition of excitement 
are especially liable to shock ; conditions of narcosis and drunkenness 
inhibit its occurrence. 

Shock is characterized chiefly by weakened energy on the part of the 
heart and irregular breathing, which lead to a decrease in the inter- 
change of gases in the tissues and to a lowering of the temperature ; as a 
result, the venous blood in persons dying of shock is lighter in color than 
the normal venous blood (Roger). The consciousness is usually pre- 
served, the skin and visible mucous membranes are pale, the pulse 
is small and markedly quickened, often irregular and intermittent. 
Further, the individual suffering from shock may be either excited, 
groan, shriek, and complain of a fearful anxiety associated with 
dyspnoea (eretJiistic shock) ; or he may lie quiet, with sunken countenance 
and exhibit evidences of great weakness of both sensory and motor func- 
tions (torpid sJiock). In severe cases death takes place from the stoppage 
of the heart and cessation of respiration. 

Shock, in being due to the over- stimulation of the peripheral nerves, 
is closely allied etiologically to the phenomenon known as syncope ; but 
the last-named condition differs essentially from shock in that its chief 
symptom is a transitory loss of consciousness, while the functions of the 
heart and respiration show no marked disturbance. Syncope is, further, 
usually preceded by prodromal symj^toms, such as dizziness, ringing in 
the ear, and darkening of the visual field, these being absent in shock. 

Not infrequently, following an injury to some part of the body, there 
may arise a more or less pronounced functional disturbance of the ner- 
vous system, which may often persist long after the local injury has 
healed, so that such disturbance is in no way dependent upon anatomical 
changes in the peripheral or central nervous system, but must be re- 



EFFECTS OF TRAUMA. 



17 



garded as piirely fimctional distiirbmice of psychics Such condi- 

tions are termed traumatic neuroses or accident nervous diseases, and 

are characterized chiefly by subjective but in part also by objective symp- 
toms. To the first belong especially pains not definitely localized at 
the seat of injury, as headache, pain in the chest, backache, difficulty 
in movement, general lassitude, inability to perform mental labor, dul- 
ness of perception, disturbances of sight, flashes before the eyes, dizzi- 
ness, restless sleep, loss of appetite, and disturbances of digestion. With 
these last symptoms are associated (Oppenheim, Striimpell) psychical 
depression of a hypochondriacal or melancholic character, irregularly 
placed areas of cutaneous anaesthesia, enf eeblement of the senses of taste, 
hearing, and smell, motor paralysis, cramps, and hypersesthesia, concen- 
tric narrowing of the visual field, pareses, muscular spasms, tremors, 
acceleration of the pulse, and tendency to sweating. 

According to the opinion of various writers, these phenomena de- 
pend essentially upon a psychical shattering of the perceptive life, a 
psychoneurosis which is less often due to the trauma and the associated 
psychical shock than to the resulting anxiety over health and business 
matters. The condition in part partakes of the nature of hysteria, as 
characterized by a disturbance of the normal relation between the men- 
tal and bodily processes ; in part of hypochondria, as recognized by the 
spontaneous occurrence of abnormal sensations ; and in part of a neuras- 
thenia, which reveals itself by the production of abnormal pathological 
sensations through slight stimulation or exertioji. If the will no longer 
controls the motor centres, hysterical paralyses arise; if the normal con- 
trol and inhibition of the will are lost, so that unreasonable will-stimuli 
are created and influence the muscles, hysterical twitchings, contract- 
ures, or convulsions take place. If a nervous stimulus arising in the 
sensory tract fails to reach the consciousness, there follows a hysterical 
anaesthesia; if there arise in the consciousness the images of expected 
or feared sensations, and if these images are intensified into actual sub- 
jective stimuli of consciousness, hysterical pains and neuralgias result 
(Striimpell). 

Rosenhach designates as kinetoses those diseases which arise when energetic and 
continuous movements of the body in one direction are changed into the opposite direc- 
tion, so that a shifting of the internal organs results. In this class belong the patho- 
logical phenomena observed in seasickness, and in the conditions caused by see-sawing, 
whirling, movement in a vertical direction, and sudden stojypage of motion. As a result of 
the rapid change in direction of bodily motion, the molecules which are moving in the 
line of the primary direction are forced to move in the opposite direction; and, ac- 
cording to Rosenbach, such a change is sufficient to cause more or less important molec- 
ular disturbance. He explains the S3'mptoms of seasickness, as, for example, the ab- 
normal secretion of the stomach, the increase of intestinal peristalsis, the vomiting, etc., 
as the results of purely mechanical influences on the tissues, and believes that the 
liver, intestine, brain, and nerve-plexuses are similarly affected through mechanical in- 
fluences acting upon their protoplasm. Further, purely psychical influences excited 
by feelings of discomfort may aid in the production of seasickness, just as disgust, 
fright, or fear may cause dizziness. 

Literature. 

(Effects of Trauma.) 

V. Bergmann: Die Lehre von den Kopfverletzungen, Stuttgart, 1880. 
Bruns: Unfallsneurosen. Eulenburg's Jahrb. , viii., 1898 (Lit.). 
Pischer: Ueber den Shock. Samml. klin. Vortr. v. Volkmann, No. 10, 1870. 
Preund: Traumatische Neurosen. Samml. klin. Vortr., No. 51, Leipzig, 1892. 
2 



18 



THE EXTRIXSIC CAUSES OF DISEASE. 



Groeningen : Ueber den Shock, Wiesbaden. 1885. 

Hober; :^Lock durch Reizung seroser Haute. Arch. f. exp. Path., 40 Bd., 1897. 

Jolly: 'rraiimatische Epilepsie. Char. -Ann., xx., 1895. 

Lejars: Les agents mecaniqiies. Path. gen. publ. par Bouchard, i., 1895. 

Oppenheim: Die traumatischen Xeurosen. Berlin, 1892. 

Roger: Choc nerveux. Arch, de phys.. v.. 1893, vi., 1891. 

Rosenbacli: Die Seekrankheit. 1Vieu. 1896; u. Eulenbur2:"s Realencyklop. xxii,^ 
1899. 

Sach.su. Freund: Die Erkrankungen des Nervensystems nach Unfallen, Berlin, 1899. 
Schultze: Ueber Xervenkrankheiten nach Trauma. D. Zeitschr. f. Xervenheilk., i. 
Seeligmiiller : Unfallnervenkraukheiten. Encvklop. Jalirb. der 2:^8. Heilkunde, 1893 
(Lit.). 

Stern: Die traumatische Entstehung innerer Krankheiten. Jena, 1900 (Lit.). 
Strumpell: Trauraat. Xeurosen. Miinch. nied. Woch., 1889: Verb. d. XII. Congr. f, 
inn. 31ed., 1893. 

3. The Origin of Disease through Intoxication. 

§ 6. By poisoning or intoxication is meant that impairment of healthy 
caused hg the injurg to a tissue, which certain substances, bg virtue of their 
chemical nature, are able to produce under certain conditions. Such sub- 
stances are termed poisons, and are derived partly from the mineral 
kingdom, partly from the vegetable, and partly from the animal king- 
dom. They may occur in a natural state or they may be produced ar- 
tificially from inorganic or organic substances, which may be either 
non-poisonous or possess quite different properties. Many of the most 
important poisons are products of either plant or animal life, and are 
formed either within the tissues of the plant or animal, or from their 
food-supply by the transformation of substances which are either inert 
or possess an entirely different action. 

The most important poisons belonging to the mineral 'kingdom or ichich are 
produced from minerals are : metallic mercury, chlorine, bromine, iodine, 
sulphur, and various combinations of these substances, different combi- 
nations of arsenic, antimony, lead, barium, iron, copper, silver, zinc, 
potassium, sodium, chromium, etc. Of the poisons containing carbon^ 
ichich are artificiallg produced, the most important are: chloroform, 
chloral hydrate, ether, alcohol, iodoform, carbon bisulphide, hydro- 
cyanic acid, potassium cyanide, oxalic acid, nitroglycerin, amyl nitrite, 
l^etroleum, carbolic acid, nitrobenzole, picric acid, and aniline. It may 
be observed in this connection that modern chemistry is constantly pro- 
ducing new substances, some of which are poisons. 

Of t\iQ poisons x^roduced bg jjlants of the higher order, those of chief im- 
portance are: the vegetable allaloids, suchasmori^hine, quinine, colchicine, 
atropine, hyoscyamine, veratrine, strychnine, curarine, solanine, nico- 
tine, digitaline, santonin, aconitine, cocaine, coniine, muscarine, and 
ergotine, all of which in relatively small doses may cause poisoning. 

The lower forms of 2)lant life, especiallg bacteria, produce an extraordi- 
narg varietg of both ])oisonous and non-poisonous substances, out of the food 
material (albuminous bodies) in ichich theg develop. Some of these sub- 
stances are similar to the vegetable alkaloids, others to the ferments^ 
and are therefore designated toxic cadaveric cdJcaloids, toxic jytomains, 
toxins, toxalbumins, and toxenzgmes (compare § 10). It may happen that 
the blood, flesh, or any organ of a healthy animal may acquire poisonous 
properties as a result of changes set up in it through the growth of bac- 
teria. Such diseases due to bacterial poisons in the food are known as 
hotulismus, sausage, meat, fish, and cheese poisoning. These conditions are 
to be explained, in part, by the growth of germs in the food-stuff and 



INTOXICATION. 



19 



the formation of toxic products out of the albuminous bodies ; in part by 
the fact that germs were present in the tissues of the animal before 
death, the animal being slaughtered while diseased, and the use of its 
flesh as food causes either poisoning or the same disease as that affect- 
ing the animal. Under certain conditions foods which are not spoiled 
may already contain bacteria, and these may develop in the intestine of 
the individual eating the food and cause poisoning through the produc- 
tion of toxins, toxalbumins, or enzymes. 

According to Lombroso, the disease pellagra, which is of common oc- 
currence in Italy, Eoumania, and Greece, is caused by the eating of 
decomposed corn. The disease Tcalzke or heri-heri, which is endemic in 
Japan, is regarded by Miura and Yamagiva as due to the extended use 
of rice which has been spoiled in drying. 

Among the animals which normally produce poisons tvithin certain tissues 
of their bodies, the best known are: serpents, toads, salamanders, fish, 
mussels, oysters, scorpions, Spanish flies, and many stinging insects. 
Certain forms of sea-fish are poisonous at all times, others only at cer- 
tain periods, and observations have been made particularly of such fish 
found in Japanese waters. According to Saotschenko, the poison of 
many poisonous fishes is secreted by certain skin-glands found at the 
roots of the dorsal and caudal fins, and may be found also in the eggs 
of such fish. According to Eemy, Miura, and Takesaki, the poison is 
secreted in the sexual glands alone in the case of the poisonous fish be- 
longing to the family Gj^mnodontes (tetrodons). According to Mosso, 
there is found in the blood-serum of eels a toxic substance (ichthytoxin) 
which, when introduced into the small intestine of animals experimen- 
tally, causes symptoms -of poisoning and may kill the animal. The ob- 
servations made of cases of poisoning from the eating of mollusks occur- 
ring some years ago at Wilhelmshafen excited general interest ; in these 
cases it was found that the eating of mussels {Mytilus eduUs) caused severe 
illness, resulting in some cases in death. 

According to M. Wolff, the liver of mussels contains the poison ; its 
action, according to Schmidtmann, Yirchow, Salkowski, and Brieger, is 
similar to that of curare. Brieger has also shown that from the poison- 
ous mussels there can be obtained basic substances closely related to 
ptomains, the basic products of decomposition. To what extent the 
causes of the production of poisons in poisonous fishes and mollusks are 
to be ascribed to normal, and to what extent to pathological processes 
of life, cannot at the present time be always decided. From the fact 
that the mussels and oysters are poisonous only in certain places where 
the water is impure, and as the starfish found in the same localities are 
similarly affected, it is probable that the poisonous action of these mol- 
lusks may in part be due to their contamination with bacteria or to the 
occurrence of certain diseased conditions. 

It is difficult to give an exact definition of poison and poisoning, since the action 
of the substances considered in this connection varies greatly according to the dose and 
attenuation, as well as the method of introduction into the tissues of the body. The 
most powerful poisons when introduced in minute doses may not only be harmless, 
but may exert a beneficial or curative effect. On the other hand, substances which are 
not usually classed with the poisons, such as the non-corrosive sodium salts, when in- 
troduced into the body in large quantities or in concentrated solutions, may produce 
effects which must be regarded as of the nature of poisoning. Further, poisons in cer- 
tain dilutions (phenol) may serve as food-material. In the definition given above I 
have followed Robert, and in the brief survey over the action of poisons contained in 
the succeeding paragraphs I have made much use of his "Textbook on Intoxications," 
published in 1893. 



20 



THE EXTRINSIC CAUSES OF DISEASE. 



Snake-poison is formed exclusively in the poison-glands located above the angle of 
the mouth. It is a greenish or yellowish tinid. the virulency of wliich is not affected by 
desiccation or preservation in alcohol. The active principle is a toxalbumin. 



Literature. 

(l7itoxicatio)i.) 

Binz, Bohm, Liebreich.: Arbeiten deutsch. Pharmakoloo;en a. d. J. 1865-1889, Ber- 
lin, 1890. 

Boehm, Naunyn, v. Boeck: Intoxicationeu. v. Ziemssen's Hdb. d. spec. Path., xv., 
1880. 

Frohner: Lehrb. d. Toxicologic f. Thienirzte. Stuttgart, 1890. 
Hofmann: Lehrb. d. gericlitl. 3Iedicin. AYien. 1895. 
Hildebrandt : Compendium der Toxicologie. Freiburg, 1893. 

Kobert: Lehrb. der Intoxicatiouen. Stuttuart. 1898; Compend. d. Toxicologie. Stutt- 
gart, 1894. 

Kunkel: Handb. d. Toxicologie, i., Jena, 1899. 

Iiewin: ^ebenwirkuug d. Arzneimittel, Berlin, 1899; Die Pfeilgifte. Yirch. Arch., 
138 Bd.. 189-1; Toxicolon-ie. Wien, 1897; Cumulative Wirkuns:. Deut. med. 
Woch., 1899. 

Loew: Naturliches System der Gifte, Miiuchen, 1893. 

Roger: Intoxications. Path. gen. publ. par Bouchard, i., Paris, 1895. 

Richardiere : Intoxications. Traite de ^ledecine, ii., 1892. 

V. Wyss: Lehrbuch der Toxicologie, Wieu, 1895. 

(Poisoning hi/ SjwiJed Foods.) 

Albrecht: Fleischvergiftung im Bezirk Sonthofen. Wochenschr f. Tliierheilk., 1878. 
Bolling-er: Leber Fleischvergiftung. Zur Aetiologie d. Infectionskrankheiten, Mlin- 
chen, 1881. 

Butter u. Huber: Die Massenerkraukungen in Wurzen, 1877. Arch. d. Heilk., xix. 
V. During: Pellagra. Eulenburg's Realeucyklop., xviii., 1898. 

van Ermengem: Des intoxications alimentaires, Bruxelles, 1895; Botulismus. Zeit. f. 
Hyg., 2(j Bd., 1897. 

Flinzer: 3Iasseuerkraukung in Chemnitz, 1879. Yierteljahrsschr. f. ger. Med., 
xxxiv.. issi. 

Husemann : Ostreismus (Austernvergiftung). Eulenburg's Jahrb., vii., 1897 (Lit.). 
Kaensche: Krankheitserreger bei Fleischvergiftung. Zeir. f. Hyg., xxii., 1896. 
Kussmaul: Vergiftung mit Schwartenmagen. Deut. Arch. f. klin. Med., iv., 1868. 
Lombroso: Die Lehre von der Pellagra, Berlin, 1898. 
Miiller: "Wurstvergiftung. Deut. Zeitschr. f. prakt. ]Med., 1875. 

Nauwerck: AVurstvergiftung. Deut. med. Wochenschr., 1886; Wiirtt. Correspbl. f. 
Aerzte, 1886. 

Schneidemuhl : Botulismus. Centralbl. f. Bakt., xxiv., 1898 (Lit.). 
Siedamgrotzky : Ueber Fleischveroiftung. Yortr. f. Thieriirzte, iii. ser., 2. H., 1880. 
Silberschmidt : Fleischvergiftung.^ Zeitschr. f. Hyg., 30 Bd.. 1899. 
Vaughan : Milk and Cheese-poisoniuir. Zeit. f. phys. Chem., 1886: Journ. of Amer. 

Med. Assn., 1887. 
Walder: Die Typhusepidemie in Kloten. Berl. klin. Woch., 1878. 
Yamagiva: Zur Kenntniss der Kakke. Yirch. Arch., 156 Bd., 1899. 
Zangger: Yergiftung durch Kaibtieisch. Arch. f. Thierheilk., 2-4 Bd., 1871. 

{Animal Foisons. ) 

Aron: Experimentelle Studien liber Schlaugengift. Zeitschr. f. klin. Med., 1883. 
Arustamoff: Ueber die Natur des Fischgiftes. Centralbl. f. Bakt., x., 1891. 
Brenning: Die Yergiftung durch Schlangen, Stuttgart, 1895 (Lit.). 
Brieger: Miesmuschelvergiftung. Biol. Centralbl., vi., 1886, u. Deut. m.ed. Woch., 
1885. 

Calmette: Yenin des serpents. Ann. de ITnst. Past., vi., 1892; viii., 1894; ix., 1895. 
Fiscliel u. Enoch: Zur Lehre von den Fischgiften. Fortschr. d. Med., x., 1893. 
Husemann: Fischgifte. Eulenburg's Realencyklop., 1895; Schlangengifte, ib., xxi., 

1H99; Thiergifte, ih., xxiv., 1900. 
Karlinski: Zur Pathologic der Schlangenbisse. Fortschr. d. Med., viii., 1890. 



POISON PRODUCING LOCAL TISSUE CHANGES. 



21 



Kaufmann : Ueber 63 Falle von Gif tsclilangenbissen. Correspbl. f . Schweiz. Aerzte, 
1893. 

Langer: Das Gift der Honigbiene. Arch. f. exp. Path., 38 Bd., 1897. 
V. Linstow: Die Giftthiere, Berlin, 1894. 

liustig-: I microorganismi del Mytilus edulis. A. p. le Scienze Med., xii., 1888. 
Mitchell : Researches upon the Venom of the Rattlesnake, Washington, 1884. 
Mitchell antl Reichert: Venoms of Poisonous Serpents, AVashington, 1886, ref. Biol. 
Central., vii., 1888. 

Miura u. Takesaki: Zur Localisation des Tetrodongiftes. Virch. Arch., 122 Bd., 1890. 
Mosso: Un veniu dans le sang des murenides. Arch. it. de Biol., xii., 1888; u. Arch. 

f. exp. Path., XXV., 1888; Du venin qui se trouve dans le sang de I'aiguille. 

Arch. it. de Biol., xii., 1889. 
Nowak: Et. des alter, prod, paries venins des serpents et des scorpions. Ann. de 

I'Inst. Past., 1898. 

Ragotzi: Wirkung des Giftes der Naja tripudians. Virch. Arch., 122 Bd., 1890. 
Roger: Intoxications. Path. gen. publ. par Bouchard, i., Paris, 1895. 
Salkowski: Miesmuschelvergiftung. Virch. Arch., 102 Bd., 1885. 
Saotschenko : Atlas des poissons veneneux, St. Petersburg, 1887. 
Schmidt: Ueb. d. Natur des Fischgiftes. Verhandl. d. X. int. med. Congr., ii., Ber- 
lin, 1891. 

Starcke : Gift der Larveu des Kafers Diamphidia locusta (Blut auflosendes Pf eilgif t 

der Kalachari). Arch. f. exp. Path.. 38 Bd., 1897. 
Virchow, Martens, Lohmeyer, Sehulze, u. Wolff: Miesmuschelvergiftung. 

Virch. Arch., 104 Bd., 1886. 
Virchow: Miesmuschelvergiftung. Berl. klin. "Woch., 1885. 

VoUmer: Ueb. d. Wirkung d. Brillenschlangengiftes. Arch. f. exp. Path., 31 Bd., 
1892. 

Wehrmann: Et. du veuin des serpents. Ann. de I'Inst. Past., xii., 1898. 
Wolff, M.: Miesmuschelvergiftung. Virch. Arch., 103 Bd., 1886; u. 110 Bd., 1887. 
See § 12 for literature of Ptomai'ns and Toxins. 

§ 7. Poisons may be divided according to their action into three 
groups: first, those producing local tissue - changes ; second, those acting 
injuriously upon the blood; third, those affecting chiefly -the nervous 
system and the heart without producing recognizable anatomical lesions. 

The poisons which cause marked local lesions injure primarily the 
tissues with which they first come into contact upon entering the body. 
If such poisons are diffused by means of the body-fluids, the most 
diverse organs and tissues may be injured ; but their action is usually 
limited to that organ in which they are stored up or through which 
they are excreted, especially the liver, intestine, and kidneys. 

The primary seat of injury is most often the mucosa of the upper 
portion of the intestinal tract and the respiratory passages, but in many 
cases the skin is first affected. Very frequently poisons, which are em- 
ployed for disinfecting, are brought into contact with wounds for the 
purpose of killing bacteria or preventing their growth, and in this way 
may cause local changes or may be absorbed and damage the internal or- 
gans or the entire body. 

The first great group of poisons belonging to this class are those which 
cause marked tissue -changes at the primary point of contact, which are 
similar to those of burns, and for this reason have been designated 
caustics or corrosives. If the action of a caustic reaches its most char- 
acteristic severity, the affected tissue Avill be wholly destroyed and con- 
verted into either a dry, hard eschar, or under certain conditions into a 
moist, soft one. If the action is of moderate intensity as the result of 
a less concentrated solution of the caustic agent, or of incomplete action 
of the chemical even when applied in strong solution or in substance, 
or because the tissue itself is more resistant as in the case of the skin, the 
changes produced are much less severe, and are characterized by red- 
ness, swelling, inflammation, and hiemorrhages. Very diverse changes 



22 



THE EXTRINSIC CAUSES OF DISEASE. 



are often found in the same organ, such as local sloughing (necroses), 
haemorrhages, inflammations, and small swellings due to local hypersemia. 
If the changes have existed for some time, the local eschars are sur- 
rounded by a more or less marked inflammatory zone, which in the case 
of certain caustics may be of very limited exent. 

The substances belonging to the class of caustic poisons are : first, the 
corrosive acids, sulphuric, nitric, hydrochloric, phosphoric, oxalic, arse- 
nic, arsenious, osmic, acetic, lactic, trichloracetic, carbolic, and salicylic 
acids; and further, the corrosive combinations of the alkalies and alka- 
line earths, potassium and sodium hydroxide (watery solutions of KOH 
and IsTaOH), caustic ammonia (solution of NH3 in water), ammonium 
carbonate, caustic lime, and barium sulphate. Belonging in this class 
are also certain corrosive salts, chiefly of the heavy metals, such as salts 
of antimony (tartar emetic and antimony trichloride), salts of mercury 
(corrosive sublimate and red precipitate), nitrate of silver, zinc chloride, 
zinc sulphate, copper sulphate and copper acetate, aluminum acetate, 
potassium chromate and bichromate, and chloride of iron. 

ThQ poisons belonging to this class derived fro^n animals are : cantharidin, 
from the beetle Lytta vesicatoria ; phrjmin, the secretion from the cutane- 
ous glands (parotid) of the toad ; the secretions from the poison-glands 
of snakes and scorpions ; the secretion of the sting-glands of bees, wasps, 
and hornets ; the secretion of the salivary glands of stinging-gnats, flies, 
and gad-flies ; and the secretion of the poison-glands of the maxillary 
palpse of spiders (tarantula) — all of which cause local necrosis or in- 
flammation. Many of the higher plants produce in their blossoms, seeds, 
stems, or roots substances which, when brought into contact with the 
tissues, cause local irritation and inflammation, as, for example, daphne, 
different forms of Ranunculus, varieties of anemone, marsh-marigold, 
different varieties of Calla, dragon-root, Croton tiglii (from the seeds of 
which croton-oil is obtained), buckthorn (Bhamnus cathartica), black 
elder {Rhamnus frangula) . 

The nature of the local changes which these substances and many 
others not mentioned here produce is naturally very varied, and is 
dependent partly upon the activity of the poison, and partly upon the 
location and manner of application. The mineral acids, solutions of 
caustic potash and mercuric chloride, when concentrated, cause marked tis- 
sue-eschars, associated with hsemorrhagic inflammations, especially when 
taken into the stomach. Through the action of acids there is a marked 
withdrawal of the alkaline constituents of the body fluids, leading to dis- 
turbances of respiration and circulation. The venom of snakes, which 
belongs to the toxalbumins, causes usually severe local inflammations 
and haemorrhages, which often extend far beyond the region of the bite ; 
and sometimes may cause also a widespread gangrene. There are also 
snake -venoms which produce only insignificant local changes, the general 
symptoms of poisoning being much more prominent. The volatile or 
gaseous poisons, which in the form of gas or vapor cause local irritation 
of the tissues, affect chiefly the mucous membranes of the eye and 
respiratory tract (irrespirable gases). To this class belong especially the 
fumes of ammonia, chlorine, sulphurous acid, nitric oxide, Ditric diox- 
ide, nitric trioxide, osmic acid, and mustard oil. The intensity of action 
of these poisons is very varied, often causing only a transitory hypertemia, 
but being able also to give rise to tissue necrosis and severe inflamma- 
tion. The irritation of the respiratory tract gives rise to coughiug and 
a spasmodic narrowing of the glottis which may interfere with breathing. 



POISONS PRODUCINa LOCAL TISSUE CHANGES. 



23 



To the local irritation and inflammation caused by these poisons at 
the primary seat of contact may he added further effects upon internal 
organs. After the absorption of these poisons into the fluids of the 
body, those organs suffer most in which the poison is stored up or 
elaborated, though organs of the most varied structure may be affected, 
as well as those not concerned in the excretion of the poison. In the case 
of certain poisons, the changes at the point of entrance are very slight and 
often not recognizable, the important anatomical lesions occurring first 
in other tissues, to which the poison has been carried by the blood. 
Finally, a given poison may act also as a nerve and heart poison, so that 
clinically the effects of this action are much more prominent than the 
local lesion. In poisoning with corrosive sublimate, cell necrosis takes 
place in the secreting part of the kidneys, and there is also severe in- 
flammation of the colon. The salts of chromic acid, cantharidin, and 
many acids cause more or less marked degeneration and inflammation in 
the secreting portion of the kidney and in the urinary passages. 

Phosphorus, arsenic, antimony, and pulegon, which have but slight 
corrosive action, produce tissue-degenerations, particularly fatty degen- 
eration, and also haemorrhages, in the liver, heart, muscles, bone-mar- 
row, and caiDillaries of different organs, these changes being particularly 
marked in cases of phosphorus poisoning. 

If an individual is exposed for months or years to the fumes of yellow 
phosphorus, there may take place an inflammation of the jaw bones lead- 
ing to necrosis, but only when the occurrence of inflammatory changes 
is favored by other causes, such as putrid decomposition in the mouth or 
the presence of decaying teeth. 

The long- continued use of silver nitrate may be followed by a deposit 
of black granules of silver in the most diverse tissues, the skin, kidneys, 
intestinal villi, and the choroid plexus. 

The venom of snakes possesses, in addition to its local effects, a para- 
lyzing action upon the nervous system and heart, and may cause death 
through paralysis of the respiratory centre. 

Soluble salts of lead when ingested may cause irritation and inflam- 
mation of the intestine, with such symptoms as vomiting, diarrhoea, 
constipation, cramps in the stomach, associated with such nervous phe- 
nomena as anaesthesia, motor paralysis, convulsions, vertigo, and loss 
of consciousness. When ingested continuously for a long time, lead 
gives rise to general disturbances of nutrition, intestinal colic, pains in 
the limbs, anaesthesias, motor parah^ses, cerebral disturbances, and kid- 
ney disease. These disturbances are without doubt dependent upon the 
distribution and deposit of lead throughout the body, leading to anatom- 
ical lesions of varied nature. 

The active principles of ergot (Secale cornutum), sphacelinic acid and 
cornutin, when taken in large doses, as when eaten in bread, cause itch- 
ing, pain, and cramps in the limbs, followed by numbness and feeling 
of cold in the toes and finger-tips, and finally there may occur a more 
or less extensive gangrene of these parts {ergotism, KrihhelJcranMeif) ; 
at the same time ulceration of the intestine may occur. In cases of 
chronic poisoning, degenerations of the spinal cord take place (Tuczek). 
The feeding of chickens with ergot causes gangrene of the comb through 
the production of stasis and hyaline thrombosis in the blood-vessels. In 
animals fed for a long time with ergot degenerative changes are found 
in the central and peripheral nervous system, in the blood-corpuscles, 
and in the endothelium of the blood-vessels (Grigorjeff). 



21 



THE EXTRINSIC CAUSES OF DISEASE. 



Literature. 

(Foisons Froducing Local Tissue- Changes.) 

Bettmann: AVirk. d. Arseniks auf Blut imd Knoclienmark. Beitr. v. Ziegler, xxiii., 
1898. 

Brouardel: Les paralysies arsenicales. Arcli. denied, exp.. viii., 1896 (Lit.). 
Coen e D'AjutoIo: Avvelenamento cronico di piombo. Beitr. v. Zieo-ler, iii., 1888. 
Eichhorst: Ueber Bleilabmung. Yirch. Arch., 120 Bd., 1890. 
Erlicki u. Rybalkin: Arseniklahmung. Arch. f. Psych., xxiii., 1892. 
Fraenkel u. Reiche: Xierenverand. nach Scliwefelsaiireveroiftung. Virch. Arch., 
131 Bd., 1893. 

Geyer: Hautverand. bei x\.rsenicismus. Arch. f. Derm., 43 Bd., 1898 (Lit.). 
Groetze: Die Bleivergitfung, Wiirzburg, 1893. 

Grig-orjeff: Mutterkornvergiftung. Beitr. v. Ziegler, xviii., 1895. 
Griinfeld: Mutterkornvergiftung. Dorpater Arbeiten, herausgeg. v. Robert, viii., 
1892. 

Hartmann: Exper. L^ntersuchungen liber Chromsaurenephritis. Inaug.-Diss., Frei- 
burg, 1891. 

Husemann: Arseuausschlilge u. Arsenvergiftung. Encyldop. Jahrb., v., 1895; 

Bleigicht, ih., 1897. 
Ipsen: Salpetersiiures-ergiftung. Yierteljahrssclir. f. ger. 3Ied., vi., 1893. 
Jacobj: Das Sphacelotoxiu. Arch. f. exp. Path., 39 Bd., 1897. 
Janowski: Die Ursacheu der Eiteruug. Beitr. v. Ziegler, xv., 1894. 
Kaufmann: Die Sublimatintoxicatiou, Berlin, 1888; u. Yirch. Arch., 117 Bd., 1889. 
V. Kahlden: Die Aetioloo-ie und Genese der acuten Xephritis. Beitr. v. Ziegler, xi,, 

1892. 

Kobert: Lehrbuch der Intoxicationen, Stuttgart, 1893. 
Kocher: Zur Kenntniss der Phosphornekrose, Berlin, 1893. 

Kockel: AVirk. v. Dampfen salpeteriger u. Untersalpetersaurc. Yierteljahrsschr. f. 
ger. 3Ied.. 1898. 

Krysinski: Pathol, u. klin. Beitrage zur Mutterkornfrage, Jena, 1888 (Lit.). 
Lang-erhans : Yeriind. der Luftwege nach Carbolsilurevergiftung. Dcut. med. TToch., 
1893. 

Lanz: Pathogenese der mcrcuriellen Stomatitis, Berlin, 1897. 

Lesser: Yeraiul. des A'erdauuugskanals durch Aetzgifte. Yirch. Arch. 83 Bd., 1881. 
Leutert: Sublimatvergiftuug. "Portschr., xiii., 1895. 
Liewin: Arsen. Euleuburg's Realencyklopiidie, ii., 1894. 

Lindemann: Yeriind. des Stoffwechsels durch Pulegou. Zcit. f. Biol., 39 Bd., 1900. 
Maier: Bleivergittung. Yirch. Arch.. 90 Bd.. 1882. 
Meiser: AVisnnVthvergiftung. Inaug.-Diss., Freiburg, 1892. 
Meyer: AVirkung dcs Phosphors. Arch. f. exp. Patli., xiv., 1881. 
Miiller: Arseiinielanose. Arch. f. Derm., 25 Bd., 1882. 

Neuberger: AA^irkung des Sublimates auf die Nieren. Beitr. v. Ziegler, vi. 1889. 
Pistorius: Acute Arsenikvergiftung. Arch. f. exp. Path., 16 Bd., 1882. 
Riess: Phosphorver2:iftuno-. "Euleub. Pealoncyklo]^ . xix., 1899. 

Schiilz: Giftiiikeit d^er PhosphorsauerstoirvrrbuKliingcn. Arch. f. exp. Path., xviii., 
18S4. 

Schultze: Peber Bleilahmung. Arch. f. Psych., 16 Bd., 1885. 

Stadelmann: Leber den IkteTUS bei Phosphorvergiftung. Arch. f. exp. Path., xxiv., 

Steinbaus: Yeraud. d. Xetzhaut durch Phosphor. Beitr. v. Ziegler, xxii., 1897. 
Tirelli: Emin livonncment par le sublime. Arch. ital. de Biol., xxvi.. 1896. 
XJllmann: Lncali-aiiou d. Quecksilbcrmctane im Orgauismus. Arch. f. Derm., Er- 
i-anzh., 1893. 

Welander: Absorption und Elimination des Quecksilbers. Arch. f. Derm., 25 Bd., 
1893. 

Westphal: L'elier Encrithalopathia saturuina. Arch. f. Psych., 19 Bd.. l^S'^. 
Winternitz: Alluemeinwirkung ortl. reizeuder Stoffe. Arch. f. exp. Path.. 35 Bd., 
1S95. 

Ziegler u. Obolonsky: AAlrkung des Arseniks u. des Phosphors. Beitr. v. Ziegler, 
ii., 1888. See also ^ 6. 

g 8. TXiQ poisons ichirh a feet the Nood chiefiy, and are therefore termed 
blood=poisons, are partly gases and pai'tly iixed substances. The latter 



POISONS AFFECTING THE BLOOD. 



25 



are absorbed chiefly from tlie intestine, but they may also enter the body 
through wounds, or they may be injected directly into the blood-vessels. 
Some of the blood-poisons may also produce local lesions in the tissue at 
point of entrance; further, there may be joined to the action on the 
blood a direct effect upon the nervous system, which under certain con- 
ditions may cause death before the action upon the blood is recogniz- 
able. Finally, it should be emphasized that the blood-changes produced 
by the poison may cause numerous secondary changes in different or- 
gans, for instance, in the kidneys, liver, intestine, and brain. 

The most important blood-poison is carhon monoxide gas, in that it 
very frequently leads to more or less serious or fatal poisoning, through 
its action on the blood. Such poisoning most often results from the car- 
bon monoxide in coal- or illuminating-gas, but may occur under other 
conditions, as in the case of the vapors produced by gun-powder or gun- 
cotton. 

The effects of the inhalation of carbon monoxide result from the com- 
bination of the gas with the haemoglobin of the blood and the formation 
of carbon-monoxide-hgemoglobin. The amount of oxygen combined 
with the haemoglobin is thereby decreased, and the taking up of oxj^gen 
is reduced, even when the respired air contains only 0.05 per cent or 
even 0.02 per cent of CO (Gruber). The red blood-cells themselves 
X3resent no changes. A sudden supply of carbon monoxide to the ner- 
vous system may cause direct injury to the nerves, giving rise to convul- 
sions and later to paralysis (Geppert). In cases of long-continued 
poisoning the displacement of the oxygen from the greater portion of 
the red cells leads to tissue -asphyxia. If the affected individual does 
not die, there may result, in addition to the poisoning, severe disturb- 
ances of nutrition, occurring especially in the nervous system. The 
poisoning itself is characterized by headache, tinnitus aurium, v ertigo, 
malaise, vomiting, fainting, convulsions, paralysis, and coma. The 
blood, as a result of the presence of carbon monoxide, becomes a bright 
violet or cherry-red color, so that the hypersemic skin and internal or- 
gans also appear bright red. 

A second not infi-equent form of poisoning is that caused by liydro- 
cyanic acid (CJSfll ) and jyotassium cyanide {GNK), the latter being much 
used in certain technical arts. In general, hydrocyanic acid is found in 
unstable combination in the leaves, bark, and seeds of many plants (bit- 
ter almonds, cherry- and peach-stones, apple-seeds, leaves of the laurel, 
bark of Primus padus, tubers of many of the Euphorbiacese, flaxseed, 
etc.). 

Hydrocyanic acid possesses a double action. In relati^^ely small 
doses it exerts a paralyzing action upon the central nervous system, 
death following in a very short time, even after a few seconds, from the 
paralysis of the^centres of respiration and circulation. In addition, 
there is an effect upon the blood and tissues, depriving them of their 
power to combine and use the oxygen brought to them (Geppert), so 
that the organs suffocate in the presence of oxygen. According to 
Kobert, a cyan-methsemoglobin is formed which is of a bright-red color, 
and gives to the hypostatic spots of the cadaver a bright red ap- 
pearance. 

A third substance belonging to this grou^D of poisons is hydrogen 
sidphide {H^8), which may be present in the gas of sewers and dung-pits. 
When inhaled in large amounts, it may cause sudden death from paraly- 
sis of the nervous system. When hydrogen sulphide is for some time 



26 



THE EXTRINSIC CAUSES OF DISEASE. 



brought into contact with blood containing oxygen (as is usually the case 
in clecomiDOsing cadavers), a sulphur-niethgemogiobiu is formed, which 
gives to the blood a greenish color. 

Carbon monoxide, hydrocyanic acid, hydrogen sulphide, aside from 
their direct action on the nervous system, produce deleterious effects, 
chiefly, according to the statements made, in decreasing the functional 
powers of the red blood- cells, by combining with their haemoglobin. 

Another large group of jwisous a feet the blood chiefly, hij the destruction 
of the red blood-cells, and the formation of methcemoglobin, a combination of 
oxygen with the hsemogiobin in the same proportion as in oxyhiemo- 
globin, but in which the oxygen is much more tirmly held than in the case 
of the latter. Such an action is produced by various oxidizing sub- 
stances (ozone, iodine, sodium hypochloride, chlorates, nitrites, and ni- 
trates) ; by reducing agents (nascent hydrogen, palladium hydride, pyro- 
gallol, pyrocatechin, hydrochinon, and alloxanthin) ; also by substances 
which have neither a reducing nor oxidizing action (salts of aniline and 
toluidin, acetanilid). In the change from hiemogiobin to methsemo- 
giobin, oxyhgemogiobin is present as an intermediate stage. 

The formation of methcemoglobin can occur either in the red blood- 
cells or in the hcemoglobin which has escaped into the blood-plasma ; but 
the destruction of the blood-cells and the escape of haemoglobin into the 
plasma are not always followed by the formation of methiiemogiobin. 
In the case of a marked destruction of red cells, as in poisoning from 
phallin, helvellic acid, arseniuretted hydrogen, only a portion of the 
hsemogiobin is changed into methcemoglobin. Hcemogiobin and oxyhse- 
nioglobin have a red color, methsemoglobin a sepia-brown. 

Dissolution of the red blood -cells and the formation of methcemo- 
globin occur in the case of a part of those poisons causing local tissue- 
changes, as in poisoning with acids, metallic salts, phosphorus, and 
arsenic, but tlie property of attacking the red cells and changing the col- 
oring-matter belongs also to a large class of other substances. 

Phallin^ a toxalbumin present in certain mushrooms {Amanita s. 
Af/ariciis phalloides), helvellic acid, contained in the fresh morel, Helvetia 
esc id (■ Ida (the poison is lost through drying), arsenmretted hydrogen 
(AsHJ, the ethereal extract of male foil, cause destruction of the red cells 
with a resulting increased formation of bile-pigment and a deposit of 
derivatives of the blood-i^igment in the \i\ev, kidneys, and boiie-marrow. 
Potassium chlorate (KC\0^) ^pyrogallol (( \H,,, [OH] J, hydrazin (K^l^ -l^KJ, 
toluylendiamin (C^H. [NH J ..CHg), :iH i-uh' nzol (C,.H,NO,), nitroglycerin 
(C3H, [NO3] amyl ^ktrite (C^H^XOJ, pin-ir acid (C" [Js^O,] ,OH), aiiiline 
(C,.H^NHJ, carbon disulphide (CS„), are distinctive in their action, in tliat 
they cause formation of methcemoglobin, sometimes with destruction of 
the red cells, at other times without. 

Large doses of potassium chlorate may cause death in a few hours, 
througli the destruction of the red blood-cells and through the action of 
the potassium, with the occurrence of vomiting, diarrhoea, dyspnoea, 
cyanosis, and cardiac insufficiency. The blood becomes chocolate-brown 
in color. In more protracted cases of poisoning by smaller doses the 
products of blood destruction are found in the si^leen, liver, bone-mar- 
row, and kidneys. The urine in these cases may vary in color from a 
reddish-brown to black (methcemoglobin). Delirium, numbness, coma, 
and convulsions occur, showing the marked involvement of the central 
nervous system. Pyrogallol produces similar symptoms. Hydiazin 
and phenylhydrazin produce multiple thrombosis, in addition to the de- 



POISONS AFFECTING THE BLOOD. 



27 



struction of red cells and formation of meth^emoglobin. In poisoning 
with tolnylendiamin the essential feature is a destruction of the red cells, 
with a deposit of iron-containing pigment in spleen, liver, and bone-mar- 
row. In cats hsemoglobiu may be excreted by way of the urine (Biondi). 
In picric-acid poisoning there occurs, in addition to the destruction of 
blood-cells and formation of methgemoglobin, a severe irritation of the 
central nervous system, characterized by violent convulsions. Aniline 
and carbon disulphide not onlj^ injure the blood, but also give rise to ir- 
ritation and paralysis of the nervous system. 

Accordiug to Kobert, ricin derived from the seeds of the castor-bean, and ahriii 
from the seeds of abrus x>recatorius, should be chissed with the blood-poisons, in that 
in the test-tube they cause an agglutination of the red cells and the formation of a 
flocculent precipitate. In animals poisoned experimentalh^ local irritations, tissue- 
degenerations and inflammations, similar to those caused by certain bacterial toxins, are 
produced, as well as disturbances in the centres of the medulla oblongata, leading to 
cessation of respiration with progressive falling of blood-pressure. Tissue-degenera- 
tions, inflammation, and haemorrhage are found, after longer action, at the point of 
application and in the intestine, where the poison is excreted. Degenerative changes 
.are also found in lymphocytes, liver and kidney cells, and heart muscle. 

Literature. 

{Blood- Poisons ; Abrin and Eicin. ) 

Afanasiew: Yergiftung mit Tolnylendiamin. Zeitschr. f. klin. Med., 6 Bd., 1883. 
Belky: Zur Kenntniss der Wirkung der gasformigen Gifte. Virch. Arch., 106 Bd., 
1886. 

Berkley: Ricin-poisoning. Trans, of the Path. Soc. of Philadelphia, xviii., 1898. 
Biondi: Experimentelle Untersuchungen uber Hamatolvse. Beitr. v. Ziegler, xviii., 
1895. 

Bohm u. Kiilz: Gif tiger Bestandtheil d. ^lorchel. Arch. f. exp. Path., 19 Bd., 1885. 
Bostroem : Intoxication durch die essbare Morchel, Leipzig, 1882. 
Cramer: Befund im Gehirn bei Kohlenoxydvergiftung. Centralbl. f. allg. Path., iv., 
1894. 

Cruz: Alt. hist, dans I'empois. par la ricine. Arch, de med. exp., xi., 1899. 
Dittrich: Ueber methamoglobinbildende Gifte. Arch. f. exp. Path., 29 Bd., 1892. 
Dreser: Zur Toxikologie des Kohlenoxyds. Arch. f. exp. Path., 29 Bd., 1891. 
Dutting": Vergiftung durch Inhalation von Arsenwasserstoff. Inaug.-Diss., Freiburg, 
1888. 

Ehrlich.: Yeratrin- und Sublimatvergiftung. Charite-Ann. , x., 1885. 
-Falkenberg: Yergift. durch Anilin, clilorsaure Salze u. Sublimat. Yirch. Arch., 123 
Bd., 1891. 

Flexner: Hist. Chang, prod, by Ricin and Abrin. Jour, of Exp. Med., 1897, ref. Cent, 
f. a. Path., 1899. ' 

Georgiewsky ; Wirkung des Extract, filicis maris aeth. Beit, von Ziegler, xxiv., 1898. 
Geppert: Ueber das Wesen der Blausaurevergiftung. Zeitschr. f. klin. Med., 15 Bd., 
1889. 

Geyer: Chron. Hautveranderungen bei Arsenicismus. Arch. f. Derm., 43 Bd., 1898 
(Lit.). 

Huber: Giftwirkung des Dinitrobenzols. Yirch. Arch., 126 Bd., 1891. 
Husemann: Pilzvergiftung. Eulenb. Realencyklop., xix., 1898 (Lit.). 
Katayama: Neue Blutproben bei Kohlenoxvd vergiftung. Yirch. Arch., 114 Bd., 
1888. 

Kobert : Lehrbuch der Intoxicationen, Stuttgart, 1893. 

Koch: Schwarzwasserfieber (Chininvergiftung). Zeit. f. Hvff., 30 Bd. ,1899. 
Lebedeflf: Morchelvergiftiing. Yirch. Arch., 91 Bd., 1883.' " 
Liewin: ^.ebenwirkung d. Arzueimittel, Berlin, 1899; Toxikologie, Yv'ien, 1897. 
Marcacci: Empoisonnement par Toxyde de charbon. Arch. ital. de Biol., xix., 1893. 
IVEarchand: Wirkung chlorsaurer Salze. Arch. f. exp. Path., 22 Bd., 1886; u. 23 Bd., 
1887. 

V. Mering: Das chlorsaure Kali, Berlin, 1885. 

Miiller: Ricinvergiftung. Arch. f. exp. Path., 42 Bd. ; u. Beit, v Ziegler, xxvii., 
1900. 



28 



THE EXTRINSIC CAUSES OF DISEASE. 



Petrone : Avvelenamento da acido pirogaliico, Catania, 1895. 
Ponfick: Morchelvergiftung. Virch. Arch., 88 Bd., 1886. 

Poelchen: Gehirnerweicliung nach Kolilendunstvergiftung. Yircli. Arch., 112 Bd., 
1888. 

Silbermann: Blutgerinnung durch chlors. Salze, Arsen, Phosphor, etc. Virch. Arch., 
117 Bd., 1889. 

Stadelmann : Vergiftung mit Toluylendiamin. Arch. f. exp. Path., 14 Bd., 1881, 16 

Bd., 1883, 23 Bd., 1887; Der Ikterus, Stuttgart, 1891. 
Stephens: Hamolytic Action of Snake Toxins. Jour, of Path., vi., 1900. 
Stockvis: Vergift. mit chlorsaurem Kali. Arch. f. exp. Path., 10 Bd., 1897; u. 21 

Bd., 1886. 

XJschinsky: SchwefelwasserstotJvergiftung. Zeitschr. f. phys. Chem,, 17 Bd., 1892. 
Werhovsky : Abrinvergiftung. Beit, v, Ziegler, xviii., 1895. 

§ 9. The last group of poisons, generally classed together as nerve 
and heart poisons, is characterized chiefly by the fact that, in spite of the 
severity of the symptoms, as shown in the form of irritations and paraly- 
ses, anatomical changes either cannot be recognized at all or are confined 
to structural changes in the protoplasm of individual nerve-cells, which 
are of similar character in the case of different poisons. This is espe- 
cially the case when the poison is quickly fatal, while if the poisoning 
runs a protracted course, or in the case of chronic poisoning from small 
doses, extending over months and years, there are very often found 
marked anatomical changes— a fact which may be taken as evidence that 
these poisons do not produce solely functional disturbances of the ner- 
vous system, but cause injury to the cell- protoi^lasm which may be mani- 
fested in the form of degenerations. 

Of the very great number of imisons icliich act esjiecially upon the ner- 
vous system and may cause death through its paralysis, the most impor- 
tant are: chloral hydrate, opium and its alkaloid morphine, cocaine, 
atropine, hyoscyamine, daturine (stramonium-atropine), nicotine, 
coniine, cicutoxin, santonin, camphor, quinine, veratrine, colchicine, 
aconitine, strychnine, cytisin, curarine, and samandarine (salamander- 
poison). 

Of the lieart-poisons, digitalin, helleborin, muscarine, and phrynin 
(poison of toads) are of special importance. 

Ohloroform {CllCh), when applied directly to the mucous membranes, causes 
local irritation and ma}' produce transitory inflammation. When convej^ed to the blood 
through inhalation or by absorption from the intestinal tract, it gives rise, after a 
short period of stimulation, to a condition of diminished irritability of the cerebral gray 
and white matter. According to Binz, the protoplasm of the ganglion-cells suffers a 
slight coagulation. Death may be caused b}' paral.ysis of the central nervous system, 
as well as by a premature heart-failure; the latter, however, occurring onl}- when the 
heart is abnormally weak or degenerated, or possibly wlien the irritation produced by 
the chloroform upon the mucous membrane of the nose causes a strong reflex stimula- 
tion of the inhibitory nerves of the heart. The long-continued use of chloroform may 
cause degenerative changes in different organs, as the heart, kidneys, liver, muscles, 
and blood. 

Ether {diefliyl ether C^HtOC^Th) acts similarly to chloroform, but is less poisonous, 
and acts less del limcntally upon the heart. 

JSitrous o.ride ( A oO) acts chiefly upon the cerebrum, lowers the sensibility of pain, 
and paralyzes consciousness; later, the action may extend to the spinal cord, the 
medulla oblongata, and the lieart. 

Alcohol {C2II5OH), after a transitory stimulation, has a depressing and paralyzing 
action upon the brain, at the same time causing a dilatation of the arteries of the skin, 
so that in intoxicated individuals severe chilling through the skin may easily occur. 
Death may take place suddenly, with symptoms similar to those of apoplexy; more 
frequently there is a gradual loss of consciousness and of sensory perception, the respira- 
tion becomes slower, the pulse small, the face cyanotic; complete coma and general 
paralysis forming the closing symptoms. The immoderate use of alcohol for months. 



NERVE AND HEART POISONS. 



29 



or years may, on the one hand, give rise to pathological deposits of fat in those regions 
where fat is normally found ; on the other hand, to fatty degeneration of glandular or- 
gans, particularly of the kidneys and liver; also degenerative atrophies of liver and kid- 
neys associated with increase of connective-tissue ; further, sclerosis and atheroma of 
the arteries, degeneration of the brain, etc., are ascribed to the action of alcohol. At 
the present time it is impossible to say in what manner, how often, and to what extent 
these changes are dependent upon the use of alcohol. It is certain, however, that 
drunkards suffer frequently from disturbances of digestion and circulation, catarrhal 
inflammations of pharynx, larynx, and bronchi, and disturbances of cerebral function; 
and that the disease of the brain known as delirium tremens, which is characterized by 
general muscular tremors, obstinate- insomnia, anxiety, and hallucinations, is especially 
to be ascribed to alcoholism. 

Gldoral hydrate {CGhCHO.ThO) causes local irritation of mucous membranes, and 
through the blood produces paralysis of the brain, spinal cord, and heart, and thus in- 
duces sleep. In fatal doses, death follows deep coma as a result of oedema of the lungs 
due to the general relaxation of the tissues. 

Opium and Morphine (CnHigJ^O^) depress the cerebral functions, thereby inducing 
sleep ; in individual cases there may be a preceding period of stimulation. Large doses 
lead to unconsciousness, paralysis of muscles, slowing and weakening of the heart's 
action, contraction of the pupils, slowing of intestinal peristalsis, diminution in the ex- 
change of gases in the blood dependent upon diminished excitability of the respiratory 
centre. There is no characteristic autopsy finding; the blood is usually dark and fluid. 
The chronic use of opium may give rise to digestive disturbances, emaciation, vertigo, 
sleeplessness, neuralgias, imbecility, impotence, weakness of the bladder, hallucination, 
tremors of the hands and feet, fever, etc., yet these symptoms may vary much in 
different individuals. In chronic morphinism the organism becomes accustomed to 
increasingly larger doses ; withdrawal of the drug causes severe nervous disturbances, 
and under certain conditions dangerous collapse. 

Cocaine {CnFhiNOi) produces peripherally a dulling of the excitability of the 
sensory nerve-endings ; centrally, first a stimulation and later a paralysis. The chronic 
use of cocaine gives rise to symptoms similar to those of chronic morphinism. 

Atropine and hyoscyamine {CnH^^J^Oa), the alkaloids which are found in the 
Solanaceae (deadly nightshade, thornapple, and henbane), cause paralysis of the periph- 
eral nerve-organs and a central stimulation, followed later by paralysis. Solutions 
of atropine introduced into the eye produce dilatation of the pupil and paralysis of ac- 
commodation for near vision, through its paralyzing action on the endings of the motor 
oculi in the iris. Atropine may further cause suppression of the secretion of certain 
glands (as the submaxillary) ; it also inhibits intestinal peristalsis. As a result of the 
action of this poison upon the brain, a condition of excitement, gayety, inclination to 
laugh, leading even to insanity and frenzy, may be produced, followed by paralysis. 
The autopsy findings are negative. 

Nicotine (CioHnJV^), a volatile alkaloid found in the tobacco plant, acts upon both 
peripheral and central nervous systems, causing nausea, salivation, vomiting, diarrhoea, 
vertigo, muscle weakness, headache, convulsions, delirium, and paralysis. Chronic 
nicotine poisoning may give rise to nervous affections and disturbances of the heart's 
action. According to Vas, there is in both chronic nicotine and alcohol poisoning a 
degeneration of the ganglion-cells characterized by a homogeneous appearance of the 
chromatin. 

Coniine (CsHnN), the alkaloid present in hemlock, causes paralysis of the periph- 
eral motor nerve-endings, first stimulating and then paralyzing the central nervous 
system. Cicutoxin, a poisonous resin obtained from the water-hemlock (Cicuta virosa) 
produces nausea, vomiting, attacks of colic, cardiac palpitation, convulsions, and un- 
consciousness. 

Santonin {CiJli^Oz) causes convulsions by its action on the brain and spinal cord, 
with benumbing of the sensorium, vertigo, vomiting, salivation, and yellow vision or 
xanthopsia, in which white is seen as yellow and blue as green. 

Quinine {CiaH'uN'iO-i), the most important of the numerous alkaloids contained in 
the bark of cinchona and other closely related plants, has a paralyzing action upon 
living protoplasm, and in relatively small doses lowers the functional capacity of the 
brain. Large doses produce death through paralysis of the centre of respiration and of 
the heart. 

Aconitine, colchicine, and mratrine produce local irritations and, later, benumbing 
of the peripheral endings of the sensory nerves. On the central nervous system the}^ 
have first a stimulating action, later a paralyzing. 

Strychnine {C'ixH-i'iN-iO 2), obtained chiefly from the plant nux vomica, causes an 
increased reflex excitability of the nerve centres, so that the slightest external stimu- 
lus may produce tetanic convulsions. Death may occur in from ten to thirty minutes 



30 



THE EXTRINSIC CAUSES OF DISEASE. 



after the first convulsion, and is the result of central paralysis, namely, of the vaso- 
motor centre. 

Cc/'i'.n'.'ie {CigBsiy)^ the active principle of the arrow-poison curare, is probably 
derived from the cortical portion of the roots of dilferent plants of the strychnia family. 
When used in small doses it paralyzes the endings of the motor nerves of the muscles. 
Larger doses cause paralysis of the central nervous system and of the vasomotor 
nerves, after a temporary stimulation. 

Bigitu.Iin and digit^tkin. two glucosides obtained from the foxglove, act as local 
irritants: after absorption they stimulate the heart, vagus-centre, and the musculature 
of the blood-vessels, so that with a slowing of the heart-beats there is an increase of 
blood-pressure. Large doses cause headache, delirium, tinnitus aurium, irregidar in- 
crease in the frequency of the heart's action, convulsions, and coma. 

Hellehorin, a glucoside obtained from hellebore, acts similarly to the preparations 
of digitalis. 

Muscarine {dHioSOz^ tii'' poison of the fly-agaric, acts as a stimulant to those 
nerve-endings Avhich are paralyzi d by atropine. The intense excitation of the inhib- 
itor}' centres of th? heart eau-es stoppage of the unparalyzed heart, and death is 
thereby produced. The general symptoms of muscarine poisoning are salivation, ver- 
tigo, anxiety, nausea, vomiting, diarrhtva. convulsions, and finally unconsciousness. 
Small doses produce a condition of excitation similar to that of drunkenness. 



The above summary of poisons, which is of necessity confined to a limited niunber, 
I have based upon the generally accepted classification, which Koln rt has also retained 
in his text-book on intoxications. A more exact knowledge of the action of poisons 
than Ave now possess will surely in the future be made a basis for a difierent classifica- 
tion. Lm ic (see literature to ^ 6) has recently attempted to make a classification of 
poisons according to their action upon the living organism, that is. upon the living- 
protoplasm. He distinguishes two great groiqis. namely. (lOui'id poisons, which in 
moderate concentration are fatal to all living oi-ganisms: and sjnri<fl pnisons. Avhich 
have no injurious effect upon certain classes of organisms. The general poisons are 
characterized chiefly by their power to change the chemical character of the active 
protein-bodies, out of which living protoplasm is formed. The\' may be classed as 
follows: (1) O.vidi-Jiifi pnif<nns (ozone, chronuc acid, manganic acid, hypermanganic 
acid, hypochlorites, hyclrogen peroxide, chlorine, bromine, iodine, jfliosphorus, arse- 
nious acid): (2) p'nsun.s Inn-ing d cit.iliitic iicdon (ethyl ether, chloroform, chloral, many 
hydrocarbons, etc.), which transh-r to the protoplasm the unstable condition of their 
molecules, and so lead to elit inic al changes in the unstable albumin : (j^) pnismis acting 
hy the production of saUs solulile mineral liases, and corrosive alkalies, alkaline 

earths, salts of the hea\ y im tals). whieli form with the protein-l)odies chemical com- 
binations of the nature of salts; (4) .s>iJ,st;t nt;,,,! pni.snns (hydroxylamin, diamide, 
pheuylhydrazin, ammonia, phenol, hydrocyanic acid, etc.), which even when greatly- 
diluted interfere with the aldehyde or aniido-grmips. The sjitcial poisons are classified 
as follows: (1) T<>.vic protcids. i.e', (a) f'/.?v///"//// /j/.v ( prodmcd liy bacteria and poisonous- 
to animals): (b) alexins and innnniut'ixins (produced in animals physiologically or 
pathologically, and poisonous for bacterial : (c) vegitahle cuzg mis (-dhrm, ricin, produced 
from piraner()gams and the higher fungi, and poisonous to animals); (d) animal enzymes 
(produced !iy Certain animals, snakes, fishes, and spiders, and poisonous to other ani- 
mals) : el) <n-g<iii(<' /"/.v.s (Strychnine, atropine, curare, etc.), having an tmexplained ac- 
tion; (3) J10(!<OUS acting indirectlv, which interfere with the processes of respiration 
(carbon monoxide, sulphites), or which act as poisons through decomposition (nitrites, 
iodine combinations), or which cause structural alterations through changes in the 
tumidity (" Quellungszustand ") of certain organized tissues (neutral alkaline salts, 
alkaline earths, oxalates). 

Literature. 

(Xerve and Heart Poisons.) 

Afanasiew: Zur Path, des acuten u. chron. Alkoholismus. Beitr. v. Ziegler, viii.^ 
1890. 

Ambrosius: Tod nach Chloroforminhalation. Virch. Arch., 138 Bd.. Suppl.. 1894. 
Binz: Das Chinin. Berlin, 1875; Alkohol. Eulenburg's Realencyklop. . iii. Aufl., 1893. 
Braun: Verand. d. Xervensystems durch chron. Alkoholintoxication, Tubingen, 1899.. 
Brouardel: Les paralysies arsenicales. Arch, de mcd. exp., viii., 1896 (Lit.). 
Demme : Ueber den Einfluss des Alkohols auf den Organismus des Kindes, Stuttgart^ 
1890. 



ORIGIN OF DISEASE THROUGH INFECTION. 



31 



Denys: Zur Kenntuiss derWirkuug des Stiyclinins. Arch. f. exp. Path., 20 Bd., 1886. 
Faust: Zur Kenntn. d. Samandariiis. Arch. f. exp. Path., 41 Bd., 1898. 
Fraenkel, E. : Veranderungen durch Chloroformnachwirkung. Virch. Arch., 127 Bd., 
1892. 

Garre : Die Aethernarkose, Tubingen, 1893. 

Goldscheider u. Flatau: Normale u. pathol. Anatomic der Nervenzellen, Berlin, 
1898. 

Husemann: Pfeilgifte. Eulenburg's Realencyklop., xviii., 1898. 
Jacottet: Et. sur les alterations des cellules nerveuses. Beitr. v. Ziegler, xxiv., 1897. 
Jakobj : Pharmakol. Unters. ilber das Colchicumgift. Arch. f. exp. Path., 27 Bd., 
1890. 

V. Kahlden: Wirkung des Alkohols auf Leber u. Xieren. Beitr. v. Ziegler, ix., 1881. 
Kappeler: Chloroform. Deutsch. Chir., Lief. 20; Arch. f. klin. Chir., 37 Bd., 
1887. 

Kobert: Muscarinwirkung. Arch. f. exp. Path., 20 Bd., 1886; Intoxicationen, Stutt- 
gart, 1893. 

Kraepelin: Psych. Wirkung des Alkohols. Mtlnch. med. Woch., 1899. 
Lewin: Die Nebenwirkung d. Arzneimittel, Berlin, 1899; Pfeilgifte. Yirch. Archiv, 
136 Bd., 1894. 

Lissauer: Unters. iiber die Wirkungend. Veratrumalkaloide. Arch. f. exp. Path., 23 
Bd., 1887. 

Mosso: Wirkung des Cocains. Arch. f. exp. Path., 23 Bd., 1887; Pflliger's Arch, 3' 
Bd., 1892. 

Ostertag": Die todtliche Nachwirkung des Chloroforms. Virch. Arch., 118 Bd., 1889.. 
PoroscMn: Verand. durch Chloroformnarkose. Cbl. f. d. med. Wiss., 1898. 
V. Schroder: Unters. iiber Morphin. Arch. f. exp. Path., 17 Bd., 1883. 
Spitzer: Darmwirkung des Opiums u. Morphins. Virch. Arch., 123 Bd., 1891. 
Strassmann : Todtliche Nachwirkung des Chloroforms. Virch. Arch., 115 Bd., 1889. 
Striimpell: Die Alkoholfrage vom arztl. Standpunkt aus. Munch, med. Woch., 
1893. 

Tillie: Ueber d. Wirkung des Curare u. seine Alkaloide. Arch. f. exp. Path., 27 Bd., 
1890. 

Tuman: Wirkung des Cocains auf psychomotor. Centren. Arch. f. exp. Path., 22 Bd., 
1887. 

Vas: Chron. Nicotin- u. Alkoholvergiftung. Arch. f. exp. Path., 33 Bd., 1894. 
Vollmer: Wirkung v. Morphin u. Atropin auf d. Athmung. Arch. f. exp. Path., 30 
Bd., 1892. 



4. Origin of Disease tlwough Infection or Farasifism. Miasms and Conta- 
gion. Vegetable and Animal Farasites. 

§ 10. As seen in the last sections (§ 6 to § 9) , there occur in the in- 
toxications certain morbid vital phenomena, which are caused by definite 
chemical substances, the mode and severity of whose action, in so far as 
the idiosyncrasy of the poisoned individual and the especial manner of 
application of the poison are not considered, depend not only upon the 
character of the poison but also ui^on the size of the dose employed. 

In those diseases which arise from infection and which are called 
infectious diseases, we have, on the contrary, to deal with morbid vital 
phenomena, which, if we disregard the susceptibility of the infected indi- 
vidual and the especial mode of entrance of the infecting material into 
the body, are dependent solely upon the character of the infecting agerd, 
while the dose is of little or no significance. 

The essential difference between intoxication and infection lies in the 
fact that in the first case there is no increase of the poison within the 
body, while in infection the harmful agent increases after its entrance into 
the organism, so that the smallest possible amount of the infective mate- 
rial may give rise to the most severe and fatal disease. The size of the 
dose of the infecting agent has an influence upon the succeeding illness 
only in so far as the probability of infection (that is, reproduction of the 
injurious agent within the body) is increased with the amount of the 



32 



THE EXTRINSIC CAUSES OF DISEASE. 



same taken into the body, and that consequently the reproduction of the 
infective agent may in shorter time reach such proportions as to give 
rise to pathological tissue -changes and symptoms, of disease. 

The injurioas agents causing the infectious diseases enter the human 
organism from the external world and give rise to an illness ivhich may 
run a loatliognomonic course ; and from the peculiarities of this course it 
may be possible to conclud.e that the disease is due to a specific organism 
possessing a characteristic action. In the case of pregnant women the 
infective agent may be transmitted from the organism of the mother to 
the foetus in utero. 

If an infectious disease attacks a great number of individuals in a 
given locality, it becomes a pestilence or an epidemic. 

Experience based upon clinical observatiou teaches us that in some 
cases the injurious agent which causes a certain infectious disease is 
active only in certain regions and infects (that is, makes ill) individuals 
who live in this region. In other cases it is seen that contact with a dis- 
eased individual, or proximity to such, or the use of some object touched 
by the affected person or contaminated in other ways — for example, 
through dejecta or through sputum — may produce the disease. Finally, 
it may also be noted that infective material develops only at certain 
times in a given locality, and only when an infected individual visits 
that particular region and through his presence leads to the production 
there of the infective material. 

From these varying conditions occasion has been taken to divide the 
agents capable of causing infection into different groups and to desig- 
nate these by particular names. If the infective agent is connected with 
a certain locality it is termed a miasm, the conception underlying this 
being that the affected region produces the injurious material. If only 
a particular region produces the infective agent, the term local miasm is 
used; but if universally present, a ubiquitous miasm. To the miasmatic 
diseases belong especially malaria, croupous pneumonia, articular rheu- 
matism, many wound- infections, septic osteomyelitis, and ulcerative endo- 
carditis. 

The conveyal of an infection from man to man directly or indirectly 
aijd its spread through houses, villages, cities, and countries is termed a 
contagium ; and it is thereby understood that the production of the in- 
fective agent takes place only in the human body, or in some lower ani- 
mal, its development and increase outside of these being impossible. To 
such contagious diseases belong smallpox, measles, scarlatina, diphtheria, 
typhus fever, recurrent fever, anthrax, hydrophobia, gonorrhoea, whoop- 
ing-cough, influenza, many catarrhs of mucous membranes, tuberculosis, 
syphilis, glanders, and leprosy. 

If an infective agent develops in a certain locality only when an in- 
fected person visits the region and thereby gives rise to an epidemic, the 
term miasmatic contagious disease is used, with the assumption that 
the infective agent had spread from the body of the first patient into the 
outer world, and had somewhere multiplied, and either alone or through 
the aid of special local influences had been able to produce in the inhab- 
itants of the region an epidemic spread of the disease. To such mias- 
matic-contagious diseases belong cholera, typhoid fever, dysentery, yel- 
low fever, and bubonic plague. 

The nature of miasmatic and contagious diseases was unknown to the 
older practitioners. The occurrence of an infectious disease as a plague 
or epidemic was explained by causes sought in peculiar cosmic or telluric 



PARASITES. 



33 



conditions, and these were designated constitutio epidemica or constitutio 
pestilens. Only in the last decade has onr knowledge of the causes and 
natm^e of the infectious diseases made true advances, and it has been 
demonstrated that the infectious diseases are parasitic diseases, the origin 
of ivliicli is to be attributed to the increase of small living organisms ivithin the 
human body. It is true that the parasitic cause has been positively demon- 
strated in only a part of the infectious diseases, but it is highly proba- 
ble that all are caused by parasites. To the hypothesis that the causes 
of infectious diseases were to be sought in living organisms, capable of 
reproduction, in a contagium animatum, the earlier investigators were led 
chiefly by the fact that the infective agent causing a certain disease 
could, when once present, constantly renew itself and indefinitely in- 
crease, so that from a single case of the disease an endless number might 
be infected ; and further that extremely small and imponderable quanti- 
ties of the infective material were sufficient for the infection of an indi- 
vidual, so that the intense effects of an infection upon the human organ- 
ism could be explained only by the assumption of an increase of the 
infective agent within the body. 

The attempt has also been made many times to explain the phe- 
nomena of infection through the action of injurious gases or soluble fer- 
ments. Such hypotheses are wholly unsatisfactory, inasmuch as they 
leave unexplained the chief phenomena of the spread and course of epi- 
demics, or the explanations adduced are open to well-founded objections. 

The parasites which cause infectious diseases belong to the lowest 
forms of plant and animal life. Among the plants the schizomycetes 
or bacteria, among the animals the minute organisms belonging to the 
protozoa, play the most important role in the production of disease. Of 
the more highly organized plants the saccharomycetes and hypho= 
mycetes may act as infective agents, but their pathological significance 
is much less than that of the bacteria. Among the animals, numerous 
worms (N^ematodes, Trematodes, Cestodes) and arthropoda (Arachnida 
and Insects) occur as human parasites, but their action is much more 
limited, and the pathological conditions produced by them are not ordi- 
narily classed as infectious diseases in the narrow sense of the term. 

For the production of a true infection, it is necessary that a given 
parasite must increase in the human body and produce a number of gen- 
erations, which spread more or less widely through the tissues. If the 
itch-mite, which produces many generations in the epidermis, be ex- 
cluded, the parasitic Schizomycetes, Saccharomycetes, and Protozoa 
alone are to be regarded as fulfilling the above condition; the higher 
animal parasites passing only a part of their life within the human body 
— that is, within the same host. Those parasites which multiply within 
the invaded organs, through the production of eggs or of matured em- 
bryos or of larvae, do not become sexually reproductive in the same 
host. 

Parasitic infection, that is, the entrance of parasites into the hmnan 
body, and their increase, can occur in almost every part of the body. The 
most common avenues of Infection are the mucous membra^ies which admit 
of access from without, especially the respiratory and intestinal tracts, 
which in particular favor the entrance of parasites. In many cases the 
parasites are contained in the food and drink, especially in water. Since 
the pathogenic organisms are for the greater part very small, and when 
suspended in the atmosphere may be carried about everywhere by means 
of the air-currents, they are often present in the respired air and so 



34: 



THE EXTRINSIC CAUSES OF DISEASE. 



reach the air-passages or aJveoJi of the lungs, where they may become at- 
tached to the walls and frequently obtain entrance into the tissues. 

Further, tcounds form a favorable place for the entrance of small 
parasites, and may be the starting-point of an infection through the en- 
trance of the latter, either from the air or through contact with con- 
taminated fluids or objects. Finally, parasites may establish them- 
selves in the uninjured skin, and, increasing, give rise to an infectious 
disease. 

The view that certain diseases, particularly the plague, were of parasitic origin, is 
verj^old, and found expression in the works of Kirclier (1602-1680), Lancisi (1654-1720), 
Linne (1707-1778), and others. It has been left to very recent times, however, to place 
the theory of the parasitic origin of disease upon a secure foundation. Though several 
decades ago Henle, Liehermeister, and others asserted that the peculiarities of infectious, 
diseases could be explained only by the assumption of a contdr/i (nu a n imatum, the es- 
tablishment of this doctrine is due to the results of the investigations of the last thirty 
years. 

The influence which climate exerts upon man is, if the influence of temperature 
be not considered, essentially dependent upon the conditions of the soil of a given re- 
gion with respect to the development of micro-organisms which are capable of causing 
disease. A rough wind}' climate maj' therefore be health}', while one that is mild and 
subject to slight variations of temperature may be unhealthy. In the case of inhabited 
regions, the question naturally arises as to the prevalence of epidemics among the in- 
habitants. Temporary changes in the injurious influences of a certain climate are de- 
pendent partly upon the fact that the pathogenic organisms do not at all times increase 
in the same ratio, and partly that the micro-organisms present in the earth do not al- 
ways get into the drinking-water or into the atmosphere, or at least obtain entrance 
into the human organism only at times. 

According to Pettenkofer, the spread of miasmatic-contagious diseases, as, for in- 
stance, cholera, cannot be explained by the fact that bacteria from the dejecta of a 
cholera patient are able to survive outside of the body for a given length of time, and 
under favorable circumstances to increase, obtain entrance into the mouth by means of 
drinking-water, food, or unclean hands, reach the intestines, and again produce an in- 
fection. On the other hand, he believes that the disease-germs on reaching the soil are 
able to form their characteristic poisons only when certain temporary local conditions 
are present in the affected region, so that the disease germs combining with an unkown 
something, that is, under the influence of the soil, must acquire a higher virulence in 
order to form the characteristic poison of the disease. The latest researches concerning 
the etiology and spread of typhoid fever, cholera, and the plague do not support this 
theory ; on the contrary, they show that the bacteria of cholera, typhoid fever, and the 
plague are sutflcient in and of themselves in given cases to produce an infection. It 
follows from what has already been said that cholera germs, when introduced into the 
intestinal canal of man or of certain experimental animals, are able to cause cholera. 



Literature. 

{Infections. ) 

Aoyama: Mitteil. ilber die Pestepidemie in Hongkong, Tokio, 1895 (ref. Cent. f. Bakt.,. 
xix.). 

Bouchard: Les microbes pathogenes, Paris, 1892. 

Charrin: L'infection. Path. gen. publ. par Bouchard, ii., Paris, 1896. 
Daubler: Grundziige der Tropenhygiene, Berlin, 1900. 
Duclaux: Le microbe et la maladie, Paris, 1886. 

Feer: Scharlach, Masern, Rotheln. Ergebn. d. allg. Path., iv., 1899. 
Fliigge: Die Mikroorganismen, Leipzig, 1896; Verbr. d. Cholera. Zeit. f. Hyg., xiv... 
1893 (Lit.). 

Galtier: Traite des maladies contagieuses des animaux domestiques, 2d ed., t. i.. 
Paris, 1891. 

Grancher, M. : Pasteur et la medecine contemporaine. Arch, de med. exp., vi. , 1894. 
Haeser: Geschichte der Medicin u. der epidemischen Krankheiten, i.-iii., Jena, 1875- 
1882. 



BACTERIA. 



35 



Hanking-: La propagation de la peste. Ann. de Tlnst. Past., xii., 1898. 
Hecker: Die grossen Volkskrankheiten des Mittelalters, her. von A. Hirsch., Berlin, 
1865. 

Henle, J.: Pathol. Untersuchungen, Berlin, 1840; Kationelle Pathologie, Braun- 
schweig, 1853. 

Hirsch., A.: Handb. der historisch-geogr. Pathologie, i. andii., Stuttgart, 1881-1886. 
Hueppe : Die Choleraepideniie in Hamburg, 1892, Berlin, 1893 ; Einfiihrung in d. 

Bakteriologie, Wiesbaden, 1896. 
Koch.: Conferenz zur Erorterung der Cholerafrage. Deut. med. Woch., 1884, 1885, 

1886; Die Cholera in Deutschland wahrend des Winters 1892-1893. Zeit. f. Hyg., 

XV., 1893. 

Koch und Gaifky: Ber. ilb. d. Thatigkeit der zur Erforschung der Cholera im Jahre- 
1883 nach Egypten u. Indien entsandten Kommission. Arb. a. d. K. Gesundheit- 
samte, iii., Berlin, 1887. 

Laveran: Les maladies epidemiques. Path, gen., ii., Paris, 1896. 

Liebermeister : Ueber die Ursachen der Yolkserkrankung., Basel, 1865. 

Loffler: Ueber die geschichtliche EntAvickelung der Lehre von den Bakterien, Leipzig, 
1887. 

Lubarsch: Zur Lehre v. d. Geschwlilsten u. Infektionskrankheiten, Wiesbaden, 1899. 
Mannaberg- : Die Malariakrankheiten, Wien, 1899. 

Marchiafava and Bignami: Malaria. Twent. Cent. Pr., xix., New York, 1900. 
Martins: Pathogenese innerer Krankheiten, i., Leipzig, 1899. 

V. Pettenkofer: Aufsatze iiber Cholera u. Typhus in d. Zeitschr. f. Biol, seit 1864; 

Arch. f. Hyg. seit 1883; Ueber Cholera. Mlinch. med. Woch., 1892. 
Rnmpf : Die Cholera indica und nostras, Jena, 1898. 
Scheube : Die Krankheiten der warmen Lander, Jena, 1900. 

Schneidemiihl : Yergleichende Pathologie d. Menschen u. d. Thiere, Leipzig, 1895- 
1899. 

Virchow: Ges. Abhandl. a. d. Gebiete d. off. Med. u. d. Seuchenlehre, i. and ii., Berlin, 
1879. 

Weichselbanm : Epidemiologic, Jena, 1899. 
See also § 12. 

§ 11. The disease=producing bacteria are extremely small, uni- 
cellular organisms, which appear in the form of little spheres (cocci )^ 
and fine, straight, or curved rods (bacilli and spirilla), frequently unit- 
ing in peculiar combinations. Some multiply in the external world, and 
only occasionally enter the human body ; others, on the contrary, are so 
constituted that they cannot reproduce in the outer world and are able to 
multiply only when in the human or animal body. The patJwgenic bac- 
teria are therefore divided into two classes, ectogenic and endogenic; the 
first is identified with the miasmatic diseases, the latter with the conta- 
gious. There is, however, no sharp division-line between these two 
classes, inasmuch as certain bacteria which ordinarily multiply only in 
the human or animal organism, may, under certain conditions, develop 
in the outside world ; so that in a certain sense a contagium becomes a 
miasm. 

On the other hand, it is not necessary for the spreading of a disease 
caused by ectogenic organisms that the Schizomycetes develop outside of 
the human body ; more frequently a direct infection from individual to 
individual takes place. For example, the bacilli of anthrax can mul- 
tiply as well in the outer world as iii the animal body, and the disease 
may be spread by direct transmission from man to man or from an ani- 
mal to man, as well as by the entrance of the bacilli into the human or 
animal body through some infected culture -medium. The cocci which 
produce suppuration, or those causing inflammation of the lungs, can 
likewise infect a healthy individual directly from the outer world where 
they have multiplied, or from another diseased individual. 

It follows therefore that no sharp line can he drawn between miasms 
and contagions or between ectogenic and endogenic bacteria. The distinction 



36 



THE EXTRINSIC CAUSES OF DISEASE. 



is of value only in that in many infections diseases one of the two forms 
of spreading predominates, and there are also infections in which, so far 
as our knowledge goes, there is but one mode of dissemination. For ex- 
ample, small-pox and measles, the infective agents of which have not yet 
been discovered, spread only by direct and indirect contagion : and it is 
also assumed that the x>oison of syphilis is not able to increase outside 
of the htiman body. 

Pathogenic bacteria may be found outside of the human body, in 
solids, liciuids, and in the atmosphere. Those forms which are able to 
multiply outside of the body (bacteria of cholera, typhoid, anthrax, sup- 
purations, actinomycosis) are found especially in water fouled by organic 
substances, or in damp earth rich in organic material or in dead animal 
or vegetable tissue containing moisture. They are besides often present 
in dry earth and dried tisstie, and can pass from these, as well as from 
fltiids, into the air, their distribtition being favored by dust, strong ctir- 
rents of air, and excessive sprinkling. In the drying of substances con- 
taining bacteria, a portion of the bacteria are killed, since they are not 
able to siu^vive complete desiccation. Many of the pathogenic bacteria 
produce resistant forms (spores) which are able to bear long- continued and 
complete drying, and therefore to retain their vitality in the air. If these 
come into contact with firm bodies or fluids and remain attached to them, 
they may survive for a long period, and under favorable conditions — that 
is, if they find proper nottrishment and stitficient moisture, and if the tem- 
perature reaches the height necessary for their develoi)ment — they may 
again multiply. 

Bacteria, which are not able to multii^ly outside of the human or 
animal body, or at least do so only under very special and rare condi- 
tions, are able to preserve themselves outside of the body for a length of 
time, only when they produce forms which survive desiccation, or are 
not killed by the chemical influences of their environment in the fluids, 
damp earth, and tissues in which they are found. For a limited time 
they may cling to the most varied substances and retain their vitality, so 
that for a certain length of time contaminated objects are capable of 
causing infection. Bacteria which are able to survive drying may be 
found in the dust of the streets, of the floors and walls of houses, as well 
as in the air itself, particularly so when the bacteria are thrown off in 
great abundance from the diseased individual in whom they have multi- 
plied. This is especially true of the bacillus of ttiberculosis, in that in 
pulmonary tuberculosis the sputum, in intestinal tuberculosis the foeces, 
and in case of tuberculosis of the urogenital tract the urine, may contain 
great numbers of the bacilli. 

Literature. 

(Distribution of Bacteria.) 

Bolton: Verhalten verschied. Bakterien im Trinkwasser. Zcit. f. Hyg., i., 1886. 
Braem: Deireneration pathog-ener Bakterien im Wasser. Beirr. v. Ziegler. ii.. 1890. 
Chantemesse : Le sol, Teau et Tair. Traite de Path, gen., ii.. Paris, 1896. 
Cornet: Die Yerbreitung der Tuberkelbacillen ausserhalb d. Korpers. Zeit. f. Hyg., 
v., 1889. 

Cramer Die AVasserversorgung von Zurich, Ziiricb, 1885. 

Emmerich.- A^^nmreiniguug der Zwiscbendecken. Fortschr. d. ]\led.. 1., 1883 

Esmarch- Der Keinigeiialt der Wande. Zeit. f. Hyg., ii., 1887. 

Flug-ge: Die Mikrooi\2:anismen, 1896: Hygiene, Leipzig, 1894. 

Fodor . Hygien. Unters. ilber Luft, Boden u. Wasser, Braunschweig, 1882. 



BACTERIAL INFECTION. 



37 



Frankel: Bakteriengelialt des Eises. Zeit. f. Hyg., i., 1886; Bakt. in verschiedenen 
Bodenschichteu, ibid., ii., 1887; Keimgehalt des Grundwassers, ibid., vi., 1889. 

Germano: Uebertragung d. Infection durcli d. Luft. Zeit. f. Hyg., 26 Bd., 1897. 

Giacosa: Lescorpusc. organises de I'air des liautes montagnes. Arch. ital. debiol., iii., 
1886. 

Gran cher et Des champ s : Recli. s. le bacille Typlnque danslc sol. Arch, demed. exp., 
i.. 1889. 

Haegler: Die chiriirg. Bedeutung des Staubes. Beitr. v. Bruns, ix., 1892. 

Hesse: Bestimmuiig der i. d. Luft entlialt. Mikroorganismen. Mitth. a. d. K. Ges.- 

Amte, ii., Berlin, 1884; Nalirungsmittel als ]!^alirboden f. Typlius u. Cliolera. Zeit. 

f. Hyg., v., 1889. 

Kammerer u. Giacomi: In der Luft entlialt. Keime. Arch. f. isxp. Path., xxi., 1886. 
Kocli; Nachweis der Bakterien in Luft, Boden u. Wasser. Fortschr. d. Med., i., 1883. 
Lustig": Diagnostik der Bakterien des Wassers, Jena, 1893. 

Petri: Leber Nachweis u. Bestimmung pflanzl. Mikroorganismen i. d. Luft. Cent. f. 
Bakt., ii., 1887. 

Sawtschenko : Beziehung d. Fliegen z. Verbreitung d. Cholera. Cent. f. Bakt., xii., 
1893. 

Soyka: Der Boden. Handb. d. Hyg. von Pettenkofer, i.. 1889. 

Straus et Dubrarry : Duree de la vie des microbes pathogenes dans I'eau. Arch, de 
med. exp., i., 1889. 

Winog-radsky : Les organismes de la nitrification. Ann. de I'lnst. Pasteur, iv. and 
v., 1890 and 1891. 

Wolifhiigel u. Riedel: Vermehrung d. Bakt. im Wasser. Arb. a. d. K. Gesundheits- 
amte, 1886. 

§ 12. The avenues of entrance for bacteria are, in general, the 
mucous membranes of the intestinal canal, respiratory tract, and the 
middle ear, the conjunctiva, the alveoli of the lungs, and open wounds. 
Through recent wounds, both pathogenic and non-pathogenic bacteria 
are rapidly taken up into the lymph and blood ; while through wounds 
showing healthy, granulating, uninjured surfaces, the entrance of many 
bacteria into the tissues is hindered. Pathogenic bacteria not infre- 
quently enter through the uninjured skin, either by way of the hair-fol- 
licles or through the sebaceous or sweat glands. Under especial condi- 
tions (coitus, surgical operations, dribbling of urine) the infection may 
take its start from the mucous membranes of the urogenital tract. Some 
infections may be transmitted by insects, which have taken up bacteria 
with the blood or secretions of a diseased individual or animal, or, hav- 
ing become contaminated externally by such, may infect an open wound 
by scraping the bacteria oft' their legs upon the exposed surface, or by 
the dii^ect introduction of germs into the skin or accessible mucous mem- 
branes during the act of stinging or sucking. If meat containing bac- 
teria be eaten, and if tlie animal while alive was affected by an infec- 
tious disease which also occurs in man, this particular disease may be 
transmitted to man, in case the bacteria had not been previously de- 
stroyed. 

Bacteria arrive at the. point of entrance, sometimes in association 
with chemically active substances, sometimes without such ; the tirst is 
more likely to occur in the intestinal tract, the second in the respiratory 
passages and in the lungs; yet chemical substances may also find their 
way into the lungs with bacteria, and bacteria may enter the intestinal 
canal without the association of chemically active material. 

The harmful chemical substances which accompany the bacteria 
may be either an accidental admixture of the food, or of the water used 
for drinking or washing or for the cleansing of wounds, or of the re- 
spired air; but they are more frequently the products of the bacteria 
themselves. All bacteria, even the non-]3athogenic, produce within the 
medium in which they grow certain changes designated as fermentation 



38 



THE EXTRINSIC CAUSES OF DISEASE. 



or decomposition processes, which stand in the closest relationship to 
their life-activity and reproduction. Among these products of chemical 
metamorphosis are many which are injurious to the organism of man and 
the higher animals, in that they are able to cause, in a manner similar to 
that of the i^oisons already mentioned, j)artly local tissue-degenerations 
and inflammations, partly blood- changes, and partly symptoms of gen- 
eral poisoning, which may be manifested in functional disturbances of 
the nerves, heart, or respiratory apparatus. The most important of 
these substances are the decomx:>osition-products of albuminoid bodies, 
the cadaveric alkaloids or ptomains, basic bodies, of which many are 
poisonous for man and are consequently called toxins. Fnrthei", active 
albuminoid bodies, the toxalbumins, occur, which are probably formed 
and cast off by the bacteria themselves (Buchner). For exainple, in 
decomposing meat the basic products, neuridin, cadaverin, putrescin, 
neurin, and methylguanidin, are formed ; of these the last three are very 
poisonous toxins. The bacillus of typhoid fever forms a toxin (typho- 
toxin), which produces paralysis and stimulates the intestinal and 
saliva] y secretions; cholera bacteria form, in addition to penta- and 
trimethylendiamin and methylguanidin, also specific toxins, which irri- 
tate the intestine, destroy the coagulability of the blood, and cause mus- 
cular spasms. The tetanus bacillus produces tetanotoxin, a toxalbumiu 
which causes violent muscle sj)asms; according to Eoux, Yersin, 
Brieger, and C. Friinkel, the diphtheria bacillus, anthrax bacillus, 
tj^phoid bacillus, cholera spirillum, and the pus-cocci form toxalbumins. 

When bacteria develop in large luimbers in the tissues, and finally 
die, the soluble substance of the bacterial cell, mycoprotein, may cause 
irritation of the surrounding pai'ts. 

If toxic bacterial products ai e introduced in considerable quantity 
into the intestinal canal or into wounds at tlie same time with bacteria, 
symptoms of poisoning may be i^roduced without a coincident infection, 
that is, without an increase of bactei'ia in the tissues. The same thing 
may also happen when poison-producing bacteria develop in the contents 
of the intestine or in wouiid-sccri^ioiis or in iieci ntic lung-tissue, and so 
multiply as saprophytes. Siu-li cases cannot strictly be i-egarded as infec- 
tions, the disease is much more to be regarded as an intoxication; but in 
such cases a sharp line between infection and intoxication cannot be 
drawn, since bacteria originally growing as saprophytes not infrequently 
enter the tissues and multiply there. 

Intestinal intoxications caused by bacterial toxins and toxaJhiimins oc- 
cur especially when animal tissues or fluids are eaten in a state of de- 
composition due to the presence of bacteria ; and to these intoxications 
belong the greater i)art of the affections termed meat-, soisaf/r-. fish-, and 
cheese-poisoning. In these cases the particular poison is eitlier taken as 
such with the food into tlie intestinal canal, or else is formed there. 
Likewise, decomposition and fermentation of the vegetable constituents 
of diet — as, for example, fermenting frnit-juices, cabbage, peas, beaiis, 
maize, rice, etc. — may have an injurious effect upon the intestine or even 
upon the entire organism, especially when eaten in lai'ge quantities or 
for a long period of time. The chronic disease known as pellagra or 
'^maidismus/^ occurring especially in Italy, Spain, Southwest France, and 
Eoumania, is an example of such a condition. It is due to the eating of 
spoiled maize (Lombroso, Tuczek) ; and is characterized by gastro-intes- 
tinal disturbances, changes in the skin, disturbances of spinal and 
cerebral functions, and geneial inarasmus. 



LACTERIAL INFECTION. 



39 



If the bacteria which have eutered the body through one of the 
above-mentioned avenues of infection are in a strict sense pathogenic, so 
that they give rise to an infection, they may increase first at the point 
of entrance, in the intestinal mucous membrane, in a wound, in the 
skin, etc. The local effects of their growth are dependent primarily 
upon the individual characteristics of the bacteria, as well as upon the 
peculiarities of the affected tissue. In general, the local action is char- 
acterized by tissue-degenerations, necrosis, inflammations, and new-for- 
mation of tissue, so that it is possible in many cases to determine the na- 
ture of the infection, that is, the species of bacteria causing the 
infection, from the character of the local changes. It is, however, 
difficult or impossible to determine in every case the exact mode of ac- 
tion of the multiplying bacteria; in general, it may be said that the 
processes of chemical metamorphosis excited by the multiplication of the 
bacteria produce certain changes in the tissue-cells, in that different sub- 
stances of active chemical nature either kill the cells, or at least induce 
degenerative changes in them, or in part excite increased cell -activity. 
In the further development of the process the substances derived from 
dead and dissolving bacteria may also produce effects upon the surround- 
ing tissue. In a certain sense, therefore, there occurs through the local 
growth of bacteria a local intoxication, which is of far greater significance 
than the withdrawal of nutritive material through the consumption by the 
bacteria of food substances. The latter is, however, not wholly without 
significance, inasmuch as the chemical changes produced by the bac- 
teria in the tissue juices often render these unfit for the nourishment of 
the tissue-cells, so that the cells suffer even when no poisonous substances 
are produced. 

The participation of the entire organism in a local bacterial infec- 
tion may be very slight or wholly absent, so that the disease appears as 
a purely local affection (tuberculosis). In other cases the toxins and 
toxalbumins formed in the local focus of infection are absorbed into the 
body fluids (i.e., into the blood), and a general intoxication (toxincemia) 
is produced ; that is, poisonous effects are exerted upon the nervous sys- 
tem, sometimes upon the blood itself and upon the heart; and the 
poisons thus taken into the body may produce demonstrable changes in 
the internal organs, particularly in the excretory glands, at times also in 
the skin. In many diseases (tetanus, typhoid fever, streptococcus and 
staphylococcus infection, diphtheria) the symptoms of poisoning are es- 
pecially prominent. 

If healing does not take place in the primary seat of infection, the 
neighboring tissues may be involved by an invasion of bacteria by con= 
tinuity. Very often the bacteria gain entrance to the lymph=yessels 
or blood=channels {hactericemia), and in this way are transported and 
spread over the entire body. The result of this metastasis of bacteria is 
the production of a lymphogenous or hsematogenous infection ; that 
is, secondary /oci of disease identical in character with the primary seat of 
infection are formed at a distance from the primary focus. In certain 
diseases (tuberculosis, suppurations, plague) the number of metastases 
is usually very great, so that many parts of the body (lymph-glands, 
liver, lung, brain, muscles, bones, kidneys, etc.) may contain diseased 
areas. On the other hand, in other infections metastasis of bacteria 
from the original focus to other organs does not occur (tetanus, diph- 
theria), or the transported bacteria cause only changes of a milder type 
(typhoid fever). 



40 



THE EXTRINSIC CAUSES OF DISEASE. 



During the transportation of bacteria through the blood-vessels, there 
is usually no increase of the bacteria in the circulating blood, the hJood 
serving only as a vehicle to carry the bacteria to other parts of the body, 
multiplication occurring first at those points where the bacteria have 
come to rest, ^^'evertheless, in certain infections (anthrax) the bacteria 
increase enormously in the circulating blood, and in this way may cause 
damage to the blood itself. Through the obstruction of small blood-ves- 
sels by the multiplying bacteria, there may be added to the intoxication 
also local disturbances of circulation. 

The metastasis of bacteria or toxic substances, or both, from a local- 
ized seat of infection, and the production thereby of secondary foci and 
symptoms of intoxication, give rise to the condition which is generallj^ 
termed sepsis. According to the predominant symptoms there may be 
distingushed a septcemia or septicemia, a pycemia and a hjmphangoitis. 
Through the combination of both the latter with septnemia, septicopycemia 
is x^i'oduced. Originally the designation septicsemia was applied to 
those cases in which a localized infection was associated with ^.putrid 
intoxication caused by bacterial poison or a toxinainkt without the spread 
of bacteria through the body. At the present time, according to the 
precedent set by Koch, Gaffky, and others, septicaemia is used to desig- 
nate the condition characterized by the entrance of both bacteria and 
their poisons into the blood, a coincident toxina^mia and bacteriiemla ; 
indeed, by many authors the pure putrid intoxication or toxiniemia is 
separated from septicaemia. 

The term pyaemia, originally signifying a metastasis of pus through 
the blood, is at present employed to designate the condition in which 
the metastasis of bacteria gives rise to the formation of metastatic ab- 
scesses. 

In septicopysemia the symptoms of toxinsemia and bacteriaemia are 
coml)iiied with the formation of metastatic foci. Lymphangoitis is an 

injiainmiition of the I ynqyh -vessels and tlirir sio'roiindings caused by trans- 
X)orted bacteria. 

Sepsis ill its different forms is most frequently caused by the true 
pyogenic o)'ganisms, staphylococcus pyogenes aureus, and the streptococcus 
pyogenes, but similar conditions also occur in infection with the pneu- 
mococcus, gonocorciis. typlioid bacillus, colon bacillus, plague bacillus, etc. 

If bacteria ai e deposited secondarily in the body-passages which are 
lined with mucous membrane, as in the res^^iratory or urogenital tract, 
they may multiply within these tracts and produce their characteristic 
pathological clianges. Likewise, tliey may multiply also within the 
large body=cavities, in the peritoneal, pleural, and subarachnoid 
spaces. In the case of an infection occurring in a pregnant woman, 
many varieties of bacteria (anthrax, symptomatic anthrax, glanders, 
recurrent fev^r, typhoid, iDueumonia, the j)yogenic bacteria) may be 
transmitted to the foetus. 

The description given above of the course of an infection may be 
taken as a general tj'pe, and many infections run such a course (typhoid, 
pycemia, erysipelas, plague, diphtheria, tetanus, tuberculosis, syphilis, 
lei)rosy, glanders, actinomycosis, etc.); but there are also many devia- 
tions from this scheme. In the first place, it not infrequently happens 
that in an infection which in general runs a typical course, the primary 
seat of infection is not demonstrable, either becanse no changes occurred 
at the x>oint of entrance, or the changes produced have since disap- 



BACTERIAL INFECTION. 



41 



peared. Sucli forms of infection are known as cryptogenic ; they may 
be lymphogenous or haematogenous. It is typical of many infections 
that the primary k^calization of the cause of the disease is not recogniz- 
able, so that general symptoms occur before local changes are demonstrable, 
and the tissue -changes occurring later have more the character of a sec- 
ondary localization of the poison of the disease. This occurs especially in a 
number of infectious diseases, the causes of which are unknown to us; 
for example, in scarlet fever, smallpox, and measles; yet in many in- 
fections whose causes are known we are not always able to discover at 
what point the first multiplication of the bacteria occurs. Thus we 
know that in relapsing fever the spirilla are found in the blood in large 
numbers at the time of the fever, but the place of their multiplication is 
unknown to us. 

Kot infrequently a secondary infection maybe joined to one already 
present. In many cases the association is entirely accidental, in other 
cases the anatomical changes produced by the first infection cause a 
local predisposition to the new invasion. To the first group would be- 
long, for instance, a croupous pneumonia occurring in an individual 
suffering with tuberculosis ; while the occurrence of an infection with 
cocci causing suppuration and septic intoxication, as in the case of 
wound-infections, in the course of typhoid, diphtheria, scarlet fever, 
dysentery, caseous ulcerating tuberculosis, etc., may be regarded as due 
to the production of local tissue -changes favoring the entrance of bac- 
teria. According to the characteristics displayed by the recent epi- 
demics of influenza in Europe, influenza is a disease which predisposes 
in a marked degree to secondary infection. In certain infections, as, 
for example, in many forms of purulent processes, the tissues may con- 
tain, even at an early stage, two or more varieties of bacteria — an asso= 
ciation of bacteria or double infection. 

It has been known for many 3- ears that during decomposition poisonous substances 
are formed. As early as 1852 Beck observed that ammonia hydrothionate, which oc- 
curs in pus and putrid ichor, possessed septic properties when injected into animals. 
Panum, in 1863, obtained from decomposing material a putrid poison, that is, a bod.y 
not destroyed by boiling and evaporation, wiiich possessed an action similar to that 
of snake-poison and the vegetable alkaloids and caused in dogs salivation, dilatation of 
the pupils, diarrhoea, fever, and severe prostration. Yon Bergmann and Sclimiedeberg 
obtained from decomposing yeast a crj^stalline body, sepsiii, which in animals produced 
the symptoms of a putrid intoxication. Senator, Ililler, and Mihiiliez extracted from 
decaying tissue-masses by means of glycerin a substance which likewise possessed a 
septic action. Billroth called this poisonous substance pritrefactive zymoid. Selmi en- 
deavored to characterize all these substances more minutely, and obtained from differ- 
ent constituents of cadavers extracts, partly soluble in ether, partly in water, which he 
recognized as fixed bases of alkaloid -like character, and which he designated as 
cadaveric alkaloids or ptotnains. Gautier, Etxrd, Zuelzer, Sonnemchein, Beclicimp, 
Schmiedeherg , Harnach, v. Nencki, Otto, Angerer, and others also found in decomposing 
tissues similar cadaveric alkaloids, which in experiments upon animals Avere partly in- 
ert, and partly toxic, producing in the latter case symptoms of poisoning similar to 
curare, morphine, and .atropine. To wn NencM (1876) is due the honor of being tlie 
first to obtain a cadaveric alkaloid in its pure form and to establish its formula; this 
was accomplished in the case of collidin, obtained from decomposing glue and albumin, 
its platinum salt crystallizing in flat needles. Following v. NencJd, Etard, Gautier, 
and Baumann, and especially Brieger, have studied ptomai'ns, the last named having 
obtained a large number of them in a pure state and determined their physiological 
action. For instance, Brieger obtained from fibrin peptone a poison (peptotoxin) 
which in animals causes symptoms of paralysis and ultimately death. From decom- 
posing horse-flesh he extracted three substances crystallizing in needles, namely, 
neuridin, nem'in, and cholin, the second of which is markedly poisonous, and, like 
muscarine, causes salivation, disturbances of circulation and respiration, contraction of 
the pupils, and clonic convulsions. From fish-flesli he obtained, besides neuridin, three 



42 



THE EXTRINSIC CAUSES OF DISEASE. 



other poisonous iKxlics: clli ylciuliaiuiii, a subsiaiicc similar in its action to muscarine, 
and u substance calicd iiadinin. Fi-oiu (h iomposinu' ^luc and cliccsc lie obtained the 
l^oison ncinin. and from decomposed vea^l dimet hy lamin. 

The majorilv of ptomains are not l>»und in t'resli tissues, audit is therefore ver}' 
probable thai tliev are (leri\-ed IVom Die split tin-' of clienn- al c. ,nd )i nations present in 
tlie liss-i.'s. Tliu's ii is |)roi)al)le lliat ciiolin is b)nne(l irom tlie sjiliii iiig of lecithin, 
and 1)\ the furlher deeompnsit ion of cholin the jtoison neuiin is formed. Choliu and 
neuridin ai'e, aeeordinii' to ///vV/av, demorisl i-al)le e\-eii in the fi'esh human bi'ain. 

After the poisonous iialiii'('' of jiart of the i)tomains iiad ])een made known tlirough 
the researches meiitir»ned aboxc, there A\as de\eloped the h iH'nl],. >i.-< that the toxic symp- 
toms ol)ser\ed in infectious diseases couhl !)e eutii'ely, or in a .^ivat measure, ascribed 
to the action of the sul)-;tances called toxins. Through the investigations of recent 
years (/A''',/. ) ilnrlimr, r,i i<n<i\ ('. //////A-e/) it has been shown that toxalbumins 

pla\- a more important I'dle than the toxins, and can therefore be regarded as thf pcrvl- 
iar' sinriiir hurl, n\(l-iinis"hs. Our knowledge of active albuminoid bodies had been 
previously co'uhned to the enzymes (pepsin," tiypsin, ptyalin, diastase), which iiroduce 
XI hvdrolvtic splitting. The active poisonous albuminoids, the toxalbumins, have been 
made known for the first time through recent investigations of the infectious diseases. 
Brii 'it r wnd Fri'i nl. fl \\o\6. the view that the toxalbumins which produce symptoms of 
intoxication are formed by the action of bacteria from the albumins of the body juices. 
Buclnier, on the contrary, beheves that they are produced by the bacterial cell itself, 
and supports this view by the fact that the diphtheria bacillus in urine containing no 
Si\.hm\\\i\ {Giiinocliet), and the tetanus bacillus in a solution of asparagin with mineral 
salts, are able to produce their characteristic toxalbumins. As in the case of the en- 
zymes, the toxalbumins in solutions lose their activity at temperatiu'es of 55 ° to 70° C. 
In the dry state they are able to withstand much higher temperatures. After injection 
into the tissues of an animal, toxalbumins do not act immediately, but after some hours 
or even after several days. In this res]3ect they differ from ordinary poisons. 

According to the experimental investigations of Paidowslqi, staphylococci injected 
subcutaneously into guinea-pigs pass very ciuickly into the blood, and are found within 
i\ (piarter of an hour in the liver, spleen, and kidneys. They remain in the blood for 
from six to twelve hours, and then disappear. In the organs where they multiply they 
may remain as long as fourteen days. Four to ten days before death they again appear 
in the blood. Streptococci pi'oduce in rabbits a general streptomycosis restdting fa- 
tally in from twenty to twenty-four hours. 

" Should the composition of the blood be altered and the blood and tissue-juices be 
contaminated by the continuous introduction of harmful substances, a condition may 
be produced which may be designated as a dyscvsLSia. iwoduced by bacteria. It is to be 
noted, however, that the term dyscrasia, which was formerly much used to designate 
changes in the constitution of the blood and hmiph, finds at the present time but little 
usage. 

Literatu re. 

{Origin of Diseases through Bacteria and Bacterial Products.) 

Baumg-arten : Der gegenwitrtige Stand der Bakteriologie. Berlin, klin. Woch., 1900. 
Behring": Die Geschichte der Diphtheric m. Berlicksichtig. d. Immunitatslehre, Leip- 
zig, 1893. 

V. Berg-mann: Das putride Gift und die putride Intoxication. Dorpat, 1868. 
Blumberg-: Putride Intoxication. Virch. Arch., 100 Bd., 1885. 

Bouchard: Actions des produits secretes par les microbes pathogenes, Paris, 1890; 

Theorie de riniection. X. intern, med. Congr., i., Berlin, 1891; Les microbes 

pathogenes, Paris, 1892. 
Brieg-er: Aetiologie des Wundstarrkrampfs. Biol. Cbl., vii., 1887; Tetanin und 

Mytilotoxin. X'irch. Arch., 112 Bd. ; Zusammeusetzung desMytiiotoxins uebst einer 

Uebersicht der bisher bekannten Ptomaine u. Toxine, ib., 115 Bd, ; Leber Ptomaine, 

i.-iii., Berlin, 1885-1886; Bakterien und Krankheitsgifte. Biol. Cbl., x., 1890; 

Bakterieno-ifte. Zeit. f. Hvg., xix., 1895: Diphtheric u. Tetanus. Deut. med. 

Woch., 18^90: Fleischvergiftung, ib., 1897. 
Brunner: Der Begriff Pyiimie u. Septhiimie, Frauenfeld, 1899. 

Bucliner: Durchtritt von Infcctiouserregern durch aie intacte Lun2:enoberfiaLhe. 

Arch. f. Hyg., 1888; Miinch. med. Woch., 1888; Leber Bakteriengifte, ibid., 1893. 
Charrin: L'infection. Traite de Path. gen. publ. par Bouchard, ii., Paris, 1896. 
Debierre: Les maladies infectieuses. microbes, ptomaines, leucomaines. Paris. 1888. 
Duclaux: Ferments et maladies, Paris, 1882: Le microbe et les maladies, Paris, 1886; 

Phenomenes generaux de la vie des microbes. Ann. de I'lnst. Pasteur, i., 1887; 

Les matieres albuminoides, ibid., v., 1891; Traite de Mikrobiologie, Paris, 1899. 



PATHOGENIC MOULDS AND FUNGI. 



43 



van Ermengem : Les iutoxications alimeutaires, Bruxelles, 1895. 
Flexner: Tne Patliology of Toxalbumins, Baltimore, 1897. 
Fliig-g-e: Die Mikiooiganismen, Leipzig, 1896. 

Friedrich: Asept. Versorgung frisclier Wunden. Arch. f. klin. Cbir., 57 Bd., 1898. 
Galfky 11. Paak: Wurst- u. Fleisclivergiftung. Arb. a. d. Kais. Gesundheitsamte, 
vi., 1890. 

Gamaleia : Les poisons bacteriens, Paris, 1893. 

Gautier : Sur les alcaloides derives de la destruction bacterienne on physiologiques des 

tissus animaux, ptomaines et leucomaines, Paris, 1886. 
Grancher: M. Pasteur et la medecine contemporaine. Arch, de med. exp., vi., 1892. 
JSalban: Resorpt. d. Bakt. bei localer Infection. Jahrb. d. K. Akad., Wien, 1896. 
Hildebrand: Eindringen pathog. Mikroorganismen von d. Lunge aus. Beit. v. Zieg- 

ler, ii., 1887. 

Hueppe: Naturwissensch. Eiuflihrung in die Bakteriologie, Wiesbaden, 1896. 
Husemann: Fleisclivergiftung. Eucykl. Jahrb., v., 1895; Ptomaine. Eulenb, 

Eucykl., xix., 1898. 
Janowski: Die Ursachen der Eiterung (Lit.). Beitr. v. Ziegler, xv., 1894. 
V. Kahlden: Sepsis. Eulenburg's Realencyklop , xxii., 1899 (Lit.). 
Koch: Untersuchungen liber Wundinfectionskrankheiten, Leipzig, 1887. 
Xruse: Die Krankheitserregung, Leipzig, 1896. 
Xievy: Sepsinvergiftung. Arch. f. exp. Pathol., 34 Bd., 1894. 

Loffier: Die geschichtliche Entwickelung der Lehre von den Bakterien, Leipzig, 1887. 
Neisser: Durchgangigk. d. Darmwand f. Bakterien. Zeit. f. Hyg., ivxii., 1896 (Lit.). 
Neusser: Die Pellagra, Wien, 1887. 

Notzel: Lifection granulirender Wunden. Fortsch., xvi., 1898. 

OrloflF: Eintrittswege der Mikrobien in den thier. Organismus. Cent. f. Bakt., iii., 1888. 
Paltauf u. Heider: Der Bacillus maidis u. seine Bezieliungen zur Pellagra. Med. 
Jahrb., 1889. 

Panum: Das putride Gift, die Bakterien, die putride Infection und die Septikiimie. 

Y\vch. Arch., CO Bd., 1874. 
Pawljowsky : Zur Frage der Infection. Zeit. f. Hyg., 33 Bd., 1900. 
Roth.: Durchlassigkeit d. Schleimhaute u. d. auss. Haut fur Bakterien. Zeit. f. Hvg., 

iv., 1888. 

Houx et Vaillard: Contr. a I'et. du tetanos. Ann. de I'lnst. Pasteur, 1893. 
Roux et Yersin: Contr. a I'et. de la diphtheric. Ann. de I'lnst. Pasteur, 1888 and 
1890. 

Romer: Infection vom Conjunctivalsack aus. Zeit. f. Hyg., 32 Bd., 1899. 
Rung-e : Die Krankheiten der ersten Lebenstage, Stuttgart, 1893. 

Schimmelbusch u. Rieker: Bakterienresorption frischer Wunden. Fortschr. d. Med., 
1895. 

Tuczek; Klin. u. anat. Studien liber Pellagra, Berlin, 1893. 
Vaug-han and Novy : The Cellular Toxins, 1902 (Lit.). 
Virchow: Traumatismus u. Infection. Virch. Arch., 162 Bd., 1900. 
Weiss: Aetiologie der Otitis media im Sauglingsalter. Beitr. v. Ziegler, xxvii., 1900. 
Woodhead: Bacteria and their Products, London, 1891. 
See also ^ 6 and 4^ 10. 

§ 13. The pathogenic moulds and fungi belong, as do the Schizomy- 
cetes, to the non-chlorophyllaceoiis thallophytee. They occur iu the 
human organism in the form of jointed or unjointed and sometimes 
branching threads or hi/phce, and short oval cells, the so-called conidia. 
At times they form fructification organs of peculiar structure. The sin- 
gle cells are much larger than those of the Schizomycetes, so that they 
may be seen with lower magnifying power. Outside of the body the 
moulds (Mucorini) develop as velvety films of different colors, on the 
surface of many organic substances and fluids, from the carbon-com- 
pounds and salts of which they derive their nourishment. The yeast- 
fungi (Saccharomycetes) are found chiefly in fluids containing sugar, and 
are the cause of the alcoholic fermentation of the same. 

The spores or conidia, which are for the greater part formed in spe- 
cial organs of fructification, but may also be developed by a simple proc- 
ess of constriction of the ends of the hyphie, pass into the air from the 
surface of the mould-film and may be widely scattered by the air cur- 



44 



THE EXTRINSIC CAUSES OF DISEASE. 



rents. Likewise, yeast-cells may be carried about in the air, in the case 
of the evaporation of a fermenting fluid and the conversion of its residue 
into dust. 

The Mucorini and the Saccharomycetes have a much less pathological 
significance than the Schizomycetes, in that only a few forms are able to 
multiply within the body, and those which do so multiply develop only 
in a very limited area, so that the disease remains a purely local one. 
Finally, they produce no poisons capable of affecting the organism as 
a whole through the blood or nervous system, but at the most only sub- 
stances which cause changes in the tissues in the immediate neighbor- 
hood of the hyphse. They can therefore produce only local infectious 
diseases. 

The avenues of entrance for these organisms are, in general, the same 
as those for the bacteria. The development of moulds is almost entirely 
restricted to regions accessible from without. Very frequently they de- 
velop only in the necrotic material lying on the surface of the affected 
area of skin or mucous membrane or wound. Thus, for example, the 
external ear, through uncleanliness, presence of cerumen, or of oil which 
has been dropped into the canal, may become the seat of a growth 
of moulds. These may develop also in necrotic areas in the lungs 
or in desquamated epithelium and food-remains in the mouth-cavity. 
Through the ingestion of fermenting fruit- juices, a further development 
of yeasts may take place in the stomach. I^ot infiequently, under 
other conditions, the stomach may contain yeasts in small numbers. The 
changes produced by the saprophytic development of the moulds and 
yeasts are in general insignificant, that of the latter being practically nil. 
Inflammatory changes may be set up by the moulds, as a result of the 
chemical changes produced in the materials affording them nutriment. 
The local action may be increased through the penetration of the hyphse 
into the living epithelium, in that the hyj)h8e in this way enter into close 
relations with the epithelium and thereby take on the nature of a para- 
sitic growth. Under certain conditions the moulds may even penetrate 
into the connective tissue, but their development there is of a very lim- 
ited character. Only in very rare cases and under special conditions 
has a metastasis of conidia through the blood or lympli been observed. 
The deposit of conidia in other organs may be followed by a develop- 
ment of hyT)hse, which may give rise to local degenerations and inflam- 
mation. From these secondary foci no further spread of the mould oc- 
curs. 

The parasitic role of the moulds is most pronounced in the case of a 
few forms which are found in the skin, developing in the epidermis and 
its adnexa, the hair and nails, and giving rise to peculiar epithelial de- 
generations and inflammations of the papillae and corium (favus, herpes 
tonsurans, pityriasis versicolor) . In rare cases yeasts may also develop 
in the deeper tissues, and cause inflammation and tissue-proliferations. 

Literature. 

{Infection by Moulds and Yeasts.) 

Baumgarten : Lelirb. d. Mykologie, Braimscbweig, 1886-1889. 
Bezold: Otomykosis. Zur Aetiologie cler Infectioiiskianklieiten, Mlinchen, 1881. 
Buschka: Ueber Hefemnykosen. Klin. Vortr., No. 18, Leipzig, 1898. 
Busse: Pathogene Helen und Schimmelpilze. Eroebn. d. allg. Patb., v., 1900. 
Cao: Oidien u. Oidiomykosen. Zschr. f. Hyg., 34 Bd., 1900 (Lit.). 



ANIMAL PARASITES. 



45 



Dubreuilh: Les moisissures parasitaires de rhoinme. Arch, de med. exp., 1891 (Lit.). 

Puclaux : Ferments et maladies, Paris, 1882 ; Le microbe et la maladie, Paris, 1886. 

V. Diiring-: Dermatomjdvosen. Eulenb. Jahrb., 1890 (Lit.). 

nttg-ge: Die Mikroorganismeu, Leipzig, 1896. 

Kehrer: Der Soorpilz, Heidelberg, 1883. 

liGber: Die Entsteliuug der Eatzlindung, Leipzig, 1891. 

Pick: Stand der Dermatomj'kosenlelire. Arch. f. Derm., xxix., 1894. 

Podak: Aspergillusmykosen. Virch. Arch., 139 Bd., 1895 (Lit.). 

Sanfelice: Pathogene Blastomj^ceten. Zeit. f. Hj'g., xxi., 1896. 

Saxer: Pneumonomykosis aspergillina, Jena, 1900. 

Schmorl: Soormetastase in der Niere. Centralbl. f. Bakt., vii., 1890. 

Siebenmann : Die Schimmelmykosen des Ohres, Wiesbaden, 1890. 

Toulerton: Pathogen. Action of Blastomycetes. Journ. of Path., vi., 1899. 

§ 14. The production of disease by animal parasites is most fre- 
quently brought about by the introduction of mature parasites, larvse, 
or eggs into the intestinal tract through the medium of the food and 
drink or by unclean fingers. This is particularly true of those parasites 
whose habitat is in the intestine or the tissues located within the body ; 
such parasites are accordingly designated as Entozoa. Parasites living 
in the outer tissues, as the skin, are termed Epizoa-j they remain either 
on the surface of the skin or penetrate into the same from without. 
The passage of parasites from the intestine into the internal tissues aud 
the changes thereby produced constitute the condition which is usually 
called, after the designation first used by Heller, an invasion-disease. 
The animal parasites for the greater part produce only local changes, 
but they can also cause symptoms of a general disease, particularly when 
the parasites increase in the body and are present in great numbers in 
the blood or certain tissues, or when they produce toxic substances. 

The parasitic protozoa are partly harmless parasites, which develop 
in the secretions of the mucous membranes without causing pathological 
changes. Other forms, on the contrary, can penetrate into the living 
tissues, increase inside of cells, and give rise to local morbid changes, 
characterized chiefly by iDeculiar new-formations of tissue (coccidia-dis- 
ease of the rabbit's liver, epithelioma contagiosum). Certain forms, 
which are probably to be classed as Sporozoa, increase in the blood, as 
inhabitants and destroyers of the red blood cells, and are the cause of 
the infectious disease known as malaria. It is not impossible that other 
infectious diseases, for example, small -pox, are caused hj parasites be- 
longing to the Protozoa. 

The parasitic worms {Nematodes, Cestodes, Trematodes) occur in 
man, partly in the adult and fully developed sexual state, and partly in 
the larval state. In the first case they are for the greater part intestinal 
parasites, which obtain nourishment from the intestinal contents, rarely 
sucking the blood from the intestinal mucosa. Fully developed worms 
are also found in other regions, as in the blood- and lymph-vessels, bile 
passages, lung, pelvis of the kidney, and in the skin. The eggs or fully- 
developed larvae produced in the body by parasitic worms are either cast 
out with the dejecta or, through active wandering or metastasis through 
the blood or lymph, finally reach other organs of the body, where they 
pass the first stage of their development. Here they remain, however, 
in a larval condition, and do not reach sexual maturity. The larvse are 
capable of further development only when they have been taken into a 
new host. 

The worms which reach their sexual maturity in the human body are 
taken in as larvae through the food and drink. Their first stage of de- 



46 



THE EXTRINSIC CAUSES OF DISEASE. 



velopment is ppssed in the great majority of cases in animals wliose flesh 
is nsed for food ; in other cases in certain of the lower animals not used 
as food. Others develop in water or dami) earth or even in the human 
intestine, so that the embryos or eggs, which pass off with the dejecta, 
develop at once in case they are again introduced into the intestinal 
tract of man. 

The worms which occur in man only in the larval condition (hydatids) 
develoi3 from eggs which have come from sexually mature worms, which 
inhabit different animals. They are taken into the intestinal tract usu- 
ally in the food or drink, but under special conditions eggs capable of 
development may be contained in the dust of the air, and, being inhaled 
and finally reaching the intestinal tract, complete the first stage of de- 
velopment. 

The intestinal parasites for the greater part produce only slight dis- 
turbances, though they may cause mechanical irritation of the intestine. 
The presence of blood-sucking worms in large numbers {Anchylostoma 
duodenale) can cause anaemia. Those parasites which enter the tissues 
may cause in their vicinity mild inflammation and proliferation of tis- 
sue, which may produce more marked clinical symptoms when the num- 
ber of the parasites (trichina-larvse) in the tissues is very great. Others 
are of pathological importance, in that they reach a large size (echino- 
coccus cysts) and thereby crowd aside and compress the neighboring 
structures. 

Otherwise their pathogenic significance depends essentially upon their 
location. A parasite situated in the muscles or subcutaneous tissue may 
cause very slight symptoms, while one in the eye, medulla oblongata, 
heart, or blood-vessels may cause severe disturbances, and under certain 
conditions death. 

The parasitic arthropoda (Arachnida and Insects) come to the human 
body partly from the outer world, partly from infected animals, and 
partly from infected human beings. They belong almost wholly' to the 
Epizoa, which have their habitat in and upon the skin and accessible 
mucous membranes (lice, bedbugs, fleas, mites) or only occasionally take 
their nourishment from the skin (gnats, gad-flies, flies), a few multiply 
either in the skin (itch-mite) or upon its surface (lice). Flies and gad- 
flies occasionally lay their eggs upon the mucous membranes or surfaces 
of wounds, and from the eggs so laid larvae may develop. The larva of 
an arachnoid (Pentastoma denticulatum) is alone found in the inter ual 
organs. In so far as the Arachnida penetrate into the tissues (epider- 
mis, hair-follicles, and sebaceous-glands), they cause irritation and in- 
flammation ; the bite of insects that suck blood is also followed by an in- 
flammation in the neighborhood of the puncture. 

Attention has recently been directed to the possibility that mos- 
quitos, stinging flies, gad-flies, bed-bugs, lice, etc., maybe the conveyers 
of an infection, in that bacteria or protozoa may by chance be attached 
to their bodies, or that in the act of sucking blood of an infected man or 
animal they may take up into their bodies either bacteria or protozoa 
and later convey them to other individuals. So far as experience goes, 
the danger of such conveyal is not very great in the case of the majority 
of the infectious diseases, since the bacteria thus taken up die after a 
time; yet it is probable that such conveyal does take place, as, for ex- 
ample, in plague, infection with pus-cocci, and anthrax. This method 
of convej'al is of chief importance in malaria, in that the pJasmodia taken 
from the blood of infected individuals by mosquitos (anopheles) undergo 



ANIMAL PARASITES: INTRINSIC CAUSES OF DISEASE. 47 



further derelop}nent in the hodi/ofthe mosquito and produce a new generation, 
ichieh through tlie bite of the mosquito is transferred to another individual, so 
that the spread of malaria is accomplished through mosquitos. Similar 
conditions exist also in the case of the tsetse-fly disease and Texas fever 
of cattle, the latter being conveyed by ticks. Further, it is claimed by 
Manson, Sonsino, and others that the infection of man with the filaria is 
also brought about through the agency of mosquitos. 

Literature. 

(Origin of Disease through Animal Paixisites.) 

Barbacci: Die Aetiologie der Malariainfection. Cent. f. path. Anat., iii., 1892. 

Blanchard: Parasites animaux. Path, gen., ii., Paris, 1896. 

Braun : Die thierischen Parasiten des Menschen, Wiirzburg, 1893. 

Celli : Die Malaria, Berlin, 1900. 

Davaine : Traite des entozoaires, Paris, 1877. 

Golgi: Malariainfection. Arch, per le Sc. med., x., 1886, audxiii., 1889; Arch. ital. de- 
biol., ix. and xiv., 1890; Beitr. v. Ziegler, iv., 1889, and vii., 1890; Zeitschr. f. 
Hyg., X.. 1891. 

Howard : Mosquitos, New York, 1901. 

Huber: Bibliographic der klin. Helminthologie, Miinchen, 1891-1895. 
Kitt: Bakterienkiinde, Wien, 1899. 

Kuchenmeister u. Ziirn : Die Parasiten des Menschen, Leipzig, 1882. 
Laveran: Du paludisme et de sou hematozoaire, Paris, 1891. 
Leuckart: Die thierischen Parasiten des Menschen, 2 x\utl., 1879-1897. 
Liihe: Ergebnisse der neueren Sporozoenforschung. Cent. f. Bakt., xxvii. and xxviii.,. 
1900. 

Mannaberg: Die Malariaparasiten, Wien, 1893; Die Malariakrankheiten, Wien, 1899. 
Muhling: Uebertraguug von Krankheitserregern durch Wanzen u. Blutegel. Cent, 
f. Bakt., XXV., 1899. 

Nuttal: Die Mosquito-Malariatheorie. C. f. Bakt., xxv. and xxvi., 1899; die Rolle der 
Insecten, Arachnoideu u. Mj^riapoden als Trager bei der Verbreitung von durch 
Bakterien u. thier. Parasiten verursachten Krankheiten. Hvgien. Rundschau, ix., 
1899, ref. Cent. f. Bakt., xxvi., 1899. 

Perroncito: I parassiti dell' uomo e degli animali utili, Milano, 1882. 

Reed: Etiology of Yellow Fever. Pan-Amer. Cong., 1901; Anier. Med., 1901; Med.. 
Rec, 1901. 

Schneidemtihl : Die Protozoen als Krankheitserreger, Leipzig, 1898. 
TJhIworm: Centralbl. f. Bakt. u. Parasitenkunde, 1887-1900. 

Ziirn : Die Schmarotzer auf und in dem Korper der Haussaugethiere, Weimar, 1882-1889.. 



II. The Intrinsic Causes of Disease. Predisposition, Idiosyncrasy, 
and Immunity. Inheritance of Pathological Conditions and 
Diseases. 

§ 15. The view is very frequently advanced that all pathological con- 
ditions are ultimately to be referred back to external causes. This is 
correct only in so far as the development of the human species, as well 
as that of the human individual, is not the result of a definite scheme of 
evolution of successive forms of animal life, but rather has been, and is 
still, purely the result of the action of external influences. If, on the 
other hand, the life of a single individual be alone regarded, there can 
be no doubt that for the origin of many pathological changes and diseases, 
certain qualities originating, partly in the congenital anlage and partly ac- 
quired in the course of life, play a role of very great importance. 

The peculiarity of somatic qualities is shown in one of two ways: 
either in a changed condition of the power of the organism to resist ex- 
ternal influences, or in that pathological changes of tissue or disturb- 



48 



THE INTRINSIC CAUSES OF DISEASE. 



ances of function arise independently of external influences. The first 
finds expression in those qualities of the body designated as predisposi- 
tion^ idiosyncrasy, and immunity-, the latter in certain inheritable^ patho- 
logical conditions and functions of single tissues and organs or of the entire 
organism, which develop from congenital anlage without the aid of external in- 
fluences. 

Predisposition and immunity play an especially important role in 
the origin of the infectious diseases. Man possesses an absolute im- 
munity or insusceptibility to many of the micro-organisms pathogenic 
for animals; as, for example, the bacteria of swine-plague, swine- 
erysipelas, symptomatic anthrax. It is, therefore, to be inferred that 
the character of his tissues and tissue-juices does not favor the entrance 
and multiplication of the organisms causing these diseases. 

On the other hand, the human race shows an especial predisposition 
or susceptibility for other diseases, such as small-pox, vaccinia, measles, 
and influenza, so that the great majority of human individuals in the 
course of life acquire these diseases. In the case of other diseases, as 
scarlet fever, pneumonia, typhoid fever, diphtheria, the susceptibility 
seems much less, but it is not possible to determine exactly to what ex- 
tent the greater rarity of these diseases is dependent upon the fact that 
the individuals not affected are not exposed to the infection. 

In the case of many infectious diseases, there is a greater suscepti- 
bility shown in childhood than in old age ; as, for example, diphtheria, 
whooping-cough, and scarlet fever. Further, there are also variations 
in the degree of susceptibility at different times, as, for example, an in- 
dividual may be exposed at certain times to measles without becoming 
infected, while at other times under similar conditions he may contract 
the disease. 

In the case of many pathogenic organisms there appears to be neces- 
sary for the entrance of infection a certain /a roH??^ condition or temporary 
increase of susceptibility. As evidence of this may be taken the fact that 
in the human intestinal canal, and especially in the mouth and throat, 
as well as in the respiratory tract, pathogenic organisms (streptococci, 
staphylococci, pneumococci, tubercle bacilli) may be present without the 
occurrence of an infection. It may also happen that cholera spirilla 
may increase abundantly in the intestine without causing marked symp- 
toms. 

Such occurrences may be explained in part by a decrease or loss of 
virulence on the part of such bacteria, but this explanation cannot be 
applied to all cases. In many instances it must be assumed that the 
harmlessness of the bacteria is due to the ability of the tissues to hinder 
their entrance into the deeper parts. In some cases this may depend 
upon the structure and organization of the tissue, in other cases chemical 
substances may have a determining influence (see § 30). In favor of the 
first assumption lies the fact that tissue -lesions, which permit of the 
entrance of bacteria, bring about an infection. A ivound, therefore, 
in whatever way produced, forms a local predisposition, and the disease, 
in such cases, bears the character of a wound=infection. Infections 
caused by pus- cocci, tubercle bacilli, tetanus bacilli, glanders, and an- 
thrax bacilli are often of this character. 

Other causes leading to an increased predisposition to infection are 
less easily recognized. It appears that severe chilling, ^Haking of cold,' ^ 
may have this effect ; also changes in the tissues due to preceding infectious 
or non-infectious local or general diseases. In the case of intestinal infec- 



PREDISPOSITION : IDIOSYNCRASY. 



49 



tions (typhoid, cholera), gastro -intestinal disturbances, diminished acidity 
of the stomach contents, overloading of the intestines, retention of the 
contents, etc. , play an important role. IN^ot infrequently it is impossible 
to determine what causes have favored the production of an infection at 
a given time. 

Special predisposition or special lessened resistance of the organ- 
ism is also not infrequently shown to other injurious agents than those 
of infectious nature. Certain individuals are less able than others to 
stand external high temperatures, particularly if at the same time bodily 
labor is performed. Of the soldiers on a march only a fraction may 
suffer from heat-stroke, although all are under the same conditions. The 
altitude at which different individuals, during mountain ascents and bal- 
loon voyages, become sensible of the deficiency of oxygen, varies greatly. 
The after-effects of chloroform ansesthesia differ greatly in different in- 
dividuals. Many individuals become exhausted through physical or 
mental labor at a time when in other individuals, under like conditions, 
no trace of such exhaustion is discoverable ; and such influences operat- 
ing daily upon a brain, in cases of especial predisposition, may lead to 
diseased conditions. 

Occasionally certain individuals show a sensitiveness toward particu- 
lar external influences, which is wholly anomalous to that usually ob- 
served, so that symptoms of disease may be caused by influences which 
ordinarily do not affect the majority of mankind. Such a peculiar sen- 
sitiveness is designated idiosyncrasy. It is exhibited particularly in 
reference to certain chemical substances, in that certain articles of food 
or drink regarded as harmless act upon such persons as poisons. The 
eating of fresh fruit or sugar or salad produces, in certain individuals, 
nausea and vomiting. Others have an aversion to partaking of dishes 
prepared from liver or kidneys, and become ill if they overcome this 
aversion and eat these foods. Others still, after eating crawfish, lobster, 
strawberries, raspberries, morels, or asparagus, are affected with urti- 
caria, a disease characterized hy an eruption of itching wheals, colic, and 
vomiting. N^ot a few persons are unable to drink boiled milk without 
unpleasant results therefrom. Alcohol, even in very small doses, may 
in certain individuals cause marked excitation, or narcosis, or remarka- 
ble disturbances of the vaso-motor system. The drinking of cocoa may 
cause cardialgia and dyspeptic symptoms. Doses of morphine or chloro- 
form, which are borne by the majority of mankind without injury, may 
cause in certain individuals severe symptoms or even death. Some in- 
dividuals show a high degree of sensitiveness, on the part of the mucous 
membranes of the respiratory tract, to the pollen of certain grasses, so 
that during the time of the hay-harvest the inhalation of the pollen 
which is widespread through the air gives rise to a catarrhal condition 
of the nose and conjunctiva, often of the larynx, trachea, and bronchi, 
which in severe cases may be associated with asthma and fever. These 
conditions are known as hay-fever, ha/y -asthma, or as pollen -diseases. 
Disinfecting fluids, corrosive sublimate or carbolic acid, in solutions 
which are ordinarily borne without discomfort, may, when applied to 
the skin of certain individuals, cause not only local disturbances of sen- 
sation and inflammation, but under certain conditions may excite an 
eczema which spreads over a large part of the body. 

On what the peculiar idiosyncrasy in individual cases depends is not 
clear. In many cases an especial excitability of the nervous system or 
of certain parts of the same may be regarded as the cause of the phe- 
4 



50 



THE INTRINSIC CAUSES OF DISEASE. 



nomenon. In acquired idiosyncrasy, as, for instance, that exhibited 
toward certain articles of food, psychical factors may play a part. 

The great importance of the part played by natural predisposition and immunity 
in the origin of infectious diseases has not only been made evident b}^ tiie study of the 
spread of epidemics among men and animals, but has received also abundant confirma- 
tion by numerous experimental investigations. If, for example, a mixture of dilferent 
bacteria be injected into an animal, only a part of these will develop and produce tissue- 
changes; the others die. If the same mixture be injected into an animal of a different 
species, the bacteria which develop are not the same as those in the first case. Further, 
a certain form of bacteria which when inoculated into a certain species of mouse in- 
variably causes death, may, when inoculated into another mouse of different species, 
be without effect. Mice are very susceptible to anthrax, rats are nearly immune. The 
poison of the so-called septicaemia of rabbits kills with absolute certainty rabbits and 
mice ; guinea-pigs and rats are immune to it, while sparrows and pigeons'are suscepti- 
ble. The spirilla of relapsing fever may be successfully inoculated only into apes. 
Gonorrhoea, syphilis, and leprosy cannot be successfully inoculated into any of the^ 
lower animals. 

In the same species, diff^erent animals of different ages exhibit differences of sus- 
ceptibility toward certain organisms. Young dogs are easily infected with anthrax 
(Koch), old ones are not. 

Different experiments have shown that an immunity toward a certain infection 
may be destroj^ed by suitable action upon the tissue {Sirotinin, ''Die Uebertragung von 
TyphusbaciJlen auf Versuchstliiere," Zeitschr. f. Hyg., i., 1886). According to Roger 
("Contribution a I'etude experimentale duciiarbon symptomatique," Revue cle med., 
i891), the natural immunity of rabbits and pigeons against symptomatic anthrax may be 
overcome, if the non-pathogenic Bacillus prodigiosus he inoculated at the same time with 
the bacillus of the disease. According to this investigator, the decomposition product, 
of the prodigiosus that is soluble in glj^cerin exerts a modifying action upon the organism. 

According to Gottstein (" Beitriige zur Lehre von der Septikamia, " Deut. med. WocJien- 
sclir., 1890), guinea-pigs may be made susceptible to the subcutaneous inoculation of 
chicken -cholera bacilli, to which tliey are naturally immune, through the injection of 
substances which destroy the red blood-cells, such as hydracetin or pyrogallol. This 
investigator concludes, therefore, that toxic substances, which render either man or ani- 
mals more susceptible to infection, act chiefly through a dissolution of the red cor- 
puscles. According to Ze(^(''Beitrage zur Immunitatslehre," Zeitschr. f. Hyg., vii., 1890), 
white mice Avhich are immune to glanders may be made susceptible to inoculations with 
the bacilli of this disease by mixing Avith their food a small quantity of phloridzin, 
which causes a toxic diabetes. 

According to Canalis and Morjnnrjo, pigeons may be made susceptible to anthrax 
through starvation. According to Lode, chilling of the body increases the suscepti- 
bility to infection. 



The especial diseases to which the neii^-horn so frequently succumb are, aside from, 
the conditions acquired during intra-uterine life, dependent partly upon a pathological 
weakness of the entire organism (especially in case of premature birth), and partly upon 
the surrounding conditions. Asphyxia, which is of such frequent occurrence, may 
arise either as the result of bodily weakness or of pathological influences exerted dur- 
ing delivery. Infectious diseases may be acquired through the stump of the cord or 
through the accessible mucous membranes and respiratory tract during birth. Haemor- 
rhages are dependent partly upon traumatic influences exerted during birth, partly 
upon distiirbances of circulation and upon infections. 

Children are, as has been shown by medical experience, more siisceptihle to many in- 
fections than adults; particularly so in the case of whooping-cough, diphtheria, measles, 
and scarlet fever. The skin of infants also offers less resistance to the entrance of pus- 
cocci tlian that of older individuals. In this connection it should be noted that the 
slight susceptibility or the immunity of many adults is dependent upon the fact that 
they ow^e tlieir immunity to attacks of such diseases during childhood. Fui-ther, it 
should be remarked that children are more exposed to certain infections, for instance, 
tuberculosis, than are adults. 

In later life haemorrhages, softening of the brain, cardiac degenerations, cancerous 
growths, and the formation of gall-stones are of especially frequent occurrence. The 
disease of the arteries known as arteriosclerosis, and also gout, may appear even in the 
late years of middle life. The predisposition in old age to certain diseases depends in 
part upon degenerative processes, associated with premature senility of the tissues ; in 
part also upon the fact that certain influences, which the years bring with them, grad- 



PREDISPOSITION AND IMMUNITY. 



51 



ually accumulate, so that finall}- the changes which they produce become so prominent 
that they lead to functional disturbances, and thereby to recognizable morbid condi- 
tions. Moreover, it is to be remarked that many pathological symptoms of old age are 
secondary diseases, which become apparent only after other tissue-changes have 
reached a certain degree. For example, senile haemorrhages, senile gangrene, degenera- 
tions of the brain and heart are dependent upon disease-processes occurring in the 
arteries. 

The predisposition of the sexes to certain diseases depends, in the first place, upon 
the especial structure and function of the sexual apparatus. The conditions of preg- 
nancy and the puerperium offer an especially favorable field for many diseases, as, for 
example, for infection through wounds. Moreover, the different relations of the sexes 
to many diseases may be explained by differences in the modes of labor and in the hab- 
its of living of the two sexes. 

Differences of predisposition of different races are shown particularly in regard to 
malaria and dysentery, toward which the negro in general shows less susceptibility 
than the European. The Japanese are said to be more susceptible than the European 
toward beri-beri. 

Literature. 

(Fredisposition and Immunity. ) 

Bourcy: Predisposition et immunite. Pathol, gen., i., Paris, 1895. 

Canalis u. Morpurg-o: Einlluss des Hungers auf die Empfanglichkeit fiir Infections- 

krankheiten. Forschr. d. Med., viii., 1890. 
Charcot: Lecons sur les maladies des vieillards, 1868. 

Ehrlich: Experimentelle Untersuchungen iiber Immunitat. Deut. med. Wochenschr., 
1891. 

Emmerich: Die Ursachen der Immunitat. Arch. f. Hyg., xii., 1891. 
d'Espine et Picot: Manuel pratique des maladies de I'enfance, Paris, 1889. 
Galli- Valeric : Immunita e resistenza alle malattie. Mil., 1897. 
Goenner : Heufieber. Correspbl. f . Schweizer Aerzte, 1897. 
Henoch : Verlesungen uber Kinderkrankheiten, Berlin, 1890. 
Hirsch: Handbuch der historisch-geographischen Pathologic, Berlin, 1881-1886. 
Hueppe: Naturwissensch. Einfiihrung in die Bakteriologie, Wiesbaden, 1896. 
Jousset: Traite de I'acclimatement et de I'acclimatation, Paris, 1884. 
Lode: Beeintlussung d. Disposit. z. Infect, durch Warmeentziehung. Arch. f. Hyg., 
28 Bd., 1896. 

Lubarsch: Untersuch. ub. d. Ursachen d. angebor. u. erworbenen Immunitat, Berlin, 
1891 ; Zur Lehre von den Geschwiilsten u. lufectionskrankheiten, Wiesbaden, 1899. 

Mag-g-elsen : Ueber die Abhangigkeit der Krankheiten von der Witterung, Leipzig, 
1890. 

Marfan: Le surmenage. Pathol, gen. de Bouchard, i., Paris, 1895. 

Martins: Pathogenese innerer Krankheiten, Leipzig, 1899 and 1900; Krankheitsursache 

u. Krankheitsanlage. Verb, der Dtsch. Ges. d. Naturforscher, Leipzig, 1898. 
Miiller: Die Krankheiten d. weibl. Korpers in ihren Bezieh. z. d. Geschlechtsfunc- 

tionen, 1888. 

Rnng-e : Die Krankheiten der ersten Lebenstage, Stuttgart, 1893. 
Riess: Heufieber. Realencylop., 1896 (Lit.). 

Stockvis: Vergleichende Rassenpathologie und Widerstandsfahigkeit des Europaers 

in den Tropen. Verh. d. X. internat. med. Congr., i., Berlin, 1891. 
Vogel: Lehrbuch der Kinderkranheiten, Stuttgart, 1890. 

Zeehnisen: Ueber Immunitat und Idiosynkrasie. Arch. f. exp. Path., 35 Bd., 1895. 

§ 16. Among the morbid conditions originating from intrinsic 
causes, that is, without the aid of specific extrinsic influences, and 

which either appear spontaneously or are developed through any ex- 
ternal influence whatsoever, there may be distinguished different groups ; 
namely, one in which the body as a whole — the constitution — is in- 
volved ; another in which only a part of the body as a system or an or- 
gan is affected ; and, finally, a third in which only a part of an organ 
presents functional or anatomical changes of a pathological nature. It 
must be noted that there is no sharp dividing line between these groups, 
inasmuch as local pathological changes may be associated with constitu- 



52 



THE INTRINSIC CAUSES OF DISEASE. 



tional conditions. Further, it is often very difficult or impossible to de- 
termine exactly what part intrinsic and what part extrinsic causes have 
taken in the production of such pathological conditions, inasmuch as 
the force of the external influence which has called the pathological pro- 
cess into activity cannot be estimated with certainty. 

Among the constitutional diseases arising from intrinsic causes 
are to be mentioned, first, the development of dwarfs and giants, dis- 
turbances of growth, the first of which is marked by an under-develop- 
ment of all the parts of the body, both of the skeleton and the soft 
parts, while the second is characterized by a growth exceeding that of 
the ordinary individual. It cannot be doubted that both dwarf and giant 
growths are often purely dependent upon a congenital tendency ; but the 
same effects can be produced, at least in so far as the inhibition of 
growth is concerned, by harmful influences exerted during the period of 
development and growth. It cannot always be told with certainty 
whether an abnormal bodilj^ growth is dependent upon a congenital ten- 
dency or upon pathological influences during the period of growth, as, 
for example, upon disturbances of growth due to disease or loss of the 
thyroid gland. 

The same difficulty is presented in cases in which the body has at- 
tained full development of stature, but manifests a general feebleness of 
constitution, as shown by its inability to withstand a great variety of 
external influences. Such condition may arise either from congenital 
defective and weak anlage or from harmful influences which have at- 
tacked the body during intra- or extra-uterine life; or further, congeni- 
tal weak anlage and external weakening influences may have affected the 
development of the individual in an equal measure. 

A further constitutional peculiarity, which is founded upon a spe- 
cial congenital anlage, is corpulence (obesity, adipositas, lipomatosis uni- 
versalis), a condition in which fat is deposited in an excessive amount, 
either in the tissues normally containing fat, or further, in regions which 
normally contain no fat, as, for example, beneath the endocardium or 
between the muscles. The increased deposit of fat is ultimately to be 
referred to a disproportion between fat-production or fat-supply and fat- 
consumption, the pathological increase of fat being at one time depend- 
ent upon an abnormal increase of fat-production, at another on a de- 
crease of fat-consumption. Daily experience teaches that the energy 
with which metabolism goes on in the body differs greatly, and changes 
also at the different periods of life, so that the normal amount of nour- 
ishment tends at one time to fatten, at another time does not. 

In the pathological condition termed obesity, which in part rests 
upon a congenital tendency, the energy of the protoplasmic forces of 
destructive metamorphosis is weakened, so that an abnormal amount of 
fat is deposited, even when only a moderate or even a decreased amount 
of nutritive material is supplied to the tissue. 

Gout, like obesity, is also a constitutional disease, which is chiefly 
dependent upon a congenital anlage and is produced essentially by in- 
trinsic causes. The exact nature of the disease is not yet known. It is 
characterized by deposits of uric acid in the tissues. According to Gar- 
rod and Ebstein, the acute attacks of gout are caused by an accumula- 
tion of uric acid which has its origin either in the kidneys or in local 
conditions. On the other hand Pfeiffer holds that the essential feature 
of the gouty tendency consists in the fact that the uric acid is produced 
in a form which is soluble only with difficulty. According to von 



PATHOLOGICAL CONDITIONS DUE TO INTRINSIC CAUSES. 53 

Noordeii, tlie formation aud deposit of uric acid is only a secondary 
process, which, is induced by the presence of a certain ferment having 
only a local action, and is consequently not dependent upon the amount 
or character of the uric acid formed in other parts of the body. 

Pathological changes arising in single systems and organs from 
intrinsic causes may occur in any part of the body, and may involve 
an entire system or organ, or only a part of one. 

In the skeleton there may occur abnormal development of single 
parts, as, for example, an abnormal smallness of the extremities (micro - 
melia) or of the head (microcephalus) in contrast to the size of the 
trunk; an abnormal over-development of a bone or group of bones 
(macrocephalus, macrodactylism, giant growth of a finger, entire foot, 
or of an extremity) ; malformations of the extremities (cleft-hand, cleft- 
foot, etc.). Occasionally supernumerary bones, as carpal bones or 
phalanges, may develop, giving rise to supernumerary fingers. Fur- 
ther, there may be developed atypical formations, such as bony out- 
growths (exostoses, hyperostoses), which may extend over the skeleton 
to a greater or less extent, originating either spontaneously or following 
some traumatism. 

In the muscular system there occur particularly pathological bony 
formations, either single or multiple (myositis ossificans), which, in the 
period of childhood, occasionally lead to a progi-essive stiffness of the 
muscles, through the transformation of muscle into bony plates. 

In the vascular system there occur either gross anatomical changes, 
such as abnormal branching of the arteries, pathological development 
of the heart, or finer changes, which reveal themselves through some 
abnormal action on the part of the circulatory apparatus or through a 
tendency to haemorrhages (hcemopJiilia) which take place spontaneously, 
that is, without our being able to demonstrate the action of some in- 
jurious influence upon the heart or blood-vessels. 

During the development of the central nervous system there may 
occur primary disturbances, which in part may manifest themselves only 
through some pathologiccd disturbance of fimction or some special predis- 
position to disease, while others are distinguished by gross anatomical 
changes, such as abnormal smallness of the brain (micrencephalon) or of 
the spinal cord (micromyelia), defective development or absence of par- 
ticular parts (see chapter on malformations), misplacement of the gray 
matter (heterotopia of the gray substance), abnormal formation of cavi- 
ties (syringomyelia), or abnormal formations of neuroglia. These dis- 
turbances may involve the functions of the sensory organs and the motor 
centres, and even to a greater extent the psychical processes. The mor- 
bid conditions known as idiocy, epilepsy, periodic and circular insanity, 
hysteria, neurasthenia, as well as paralysis, mania, melancholia, and 
dementia, may have their origin in a congenital predisposition. Ee- 
cently the tendency to crime has also been ascribed to a congenital pre- 
disposition, and Lombroso, in particular, has endeavored to prove that 
the man who lives only through crime and for crime, the Homo deUn- 
quens, is a congenital criminal — that is, a man who suffers from bodily 
and mental abnormalities, who possesses other physical and psychical 
characters than the normal man or even than one who is simply men- 
tally unbalanced, in that he presents the symptoms of a form of degener- 
ation tending in a well-defined direction. According to Lombroso, a 
subnormal development of the anterior half of the cranium, associated 
with a corresponding lack of development of the anterior portion of the 



54 



THE INTRINSIC CAUSES OF DISEASE. 



cerebrum, iu connection with an over-development of the posterior por- 
tion, produces a feebler development of the intelligence and of the moral 
sense, and favors a strongly developed instinct-life. Benedikt even goes 
so far as to maintain that the criminal possesses a peculiar configuration 
of the cerebral convolutions, similar in type to those of beasts of prey. 

The views of Lombroso and Benedikt have met with much opposi- 
tion, and have been attacked as incorrect. There can be no doubt that 
there does not exist a degenerate species of the human race, which is 
characterized by such anatomical peculiarities as to make it possible for 
us to distinguish a class of Homo deliiiqiieiis from that of Homo sapiens. 
All the somatic peculiarities regarded as characteristic of the criminal 
type — as, for example, the beast-of-prey type of cerebral convolutions, 
slightly developed frontal brain, receding forehead, massiveness of the 
lower jaw, prognathia, asymmetry of the cranium, marked prominence 
of the arcus superficialis and arcus frontalis, pathological conformations 
of the skull, etc. — while relatively frequent in criminals, are also far 
from being infrequent iu normal men. On the other hand, it is not to 
be doubted that the tendency to crime is very frequently dependent upon 
a congenital predisposition having its seat in some special organization 
of the central nervous system. In this respect the criminal resembles 
the insane individual; further, mental diseases — for example, epilepsy 
and hysteria — are often observed iu criminals. 

Pathological cerebral f unctions may develop primarily in individuals 
possessing such morbid predispositions — that is, without external influ- 
ences playing any part in the production of the disturbance, so that the 
person concerned may manifest pathological disturbances of cerebral 
functions without the concurrence of any exterjial injury, either during 
the period of development and growth or later. On the other hand, in 
other cases, external influences — such as mental work, sorrow, care, 
psychical irritation, disease, etc. — are the causes which give rise to the 
particular illness — that is, to the occurrence of pathological brain or 
spinal-cord functions. In these cases the inherited tendency consists 
only in an abnormal weakness, a predisposition to disease of the central 
nervous system, so that insignificant influences which would produce no 
recognizable effects upon a normal individual are sufficient to excite the 
morbid phenomena. Since many influences, as diseases, infections, 
psychical irritations, are adequate under certain conditions to produce 
mental diseases in individuals who must be regarded as normal, it is 
clear that in many instances it is difficult and often impossible to deter- 
mine what part the intrinsic causes — the inherited predisposition — and 
what part the extrinsic causes have had in the production of a disease 
of the central nervous system. 

In the case of the peripheral nerves, it is especially their connective- 
tissue elements which often take on a pathological activity of growth 
under the influence of intrinsic causes. This activity may manifest it- 
self partly in the form of diffuse thickenings (fibromatosis of the nerves), 
which are situated either along the course of those nerves large enough 
to be dissected with the knife or along the finer nerves, often in large 
numbers through the entire nervous system, and occasionally involving 
the entire territory of the peripheral nerves, the skin being most fre- 
quently affected (multiple fibromata of the skin). In individual cases 
the fibromatosis of the nerves is associated with an increase in the num- 
ber of nerve-fibres, so that within a given area of nerve-distribution 
there will be found a great increase of nerve-fibres, thickened through a 



PATHOLOGICAL CONDITIONS DUE TO INTRINSIC CAUSES. 



55 



pathological increase of the endoneurium and for the greater part twisted 
and wound into serpentine forms (cirsoid neuroma, plexiform neuroma). 
Among the pathological conditions of the visual apparatus are to 

be mentioned in particular dyschromatopsia and achromatopsia, con- 
genital partial or total color-blindness, which are frequently spoken of 
as Daltonism, and are characterized by a want of perception for certain 
colors (most frequently for red and green) or for all the colors. In this 
same category belongs further the typical pigment degeneration of the 
retina, in which there occurs a peculiar spotted, black pigmentation of 
the retina, associated with a diminution of central sharpness of vision 
and light-perception, with a narrowing of the visual field. Finally, 
certain forms of myopia, also albinism (absence of pigment in the 
choroid), the latter condition also involving the structures of the skin, 
are to be considered in this connection. 

Of intrinsic conditions of the auditory apparatus deaf -mutism is of 
chief importance ; this condition, in part at least, is dependent upon a 
primary disturbance of develoi3ment. Further, certain malformations 
of the external ear fall into this class. 

In the skin and subcutaneous connective tissue new-growths may 
develop from congenital anlage, consisting of proliferations, sometimes 
of connective tissue, at other times of epithelium. They often involve 
particular parts of the skin, as the cutaneous nerves, blood-vessels, 
lymph-vessels, or the adipose tissue. When occurring as extensive 
thickenings of the skin and subcutaneous tissue, they constitute the 
foundations of the conditions known as fibromatous, neuromatous, 
haemangiomatous, lymphangiomatous, and lipomatous elephantiasis. As 
circumscribed growths they are known as birth-marks, fleshy moles, 
lentigines, freckles, and tumors of the blood- and lymph -vessels. The 
epithelial hypertrophies give rise to those conditions designated as fish- 
scale disease or ichthyosis, ichthyotic warts, and cutaneous horns. 

In addition to the pathological conditions which have been mentioned, 
there are also malformations of the body (see chapter on malforma- 
tions) or also of internal organs which must be regarded as primary— 
i.e., which are not produced by injurious influences exerted upon the 
developing foetus. Finally, many forms of tumors (see chapter on 
tumors) are to be placed in this class, particularly those which are found 
to be already developed at birth or which develop during childhood. 

Literature. 

{Diseases Arising from Intrinsic Causes.) 

Anton: Die Aufgaben d. Psycliiatrie u. d. Lelire v. d. Vererbung v. Nervenkrank- 

heiten, Wien, 1892. 
Baer: Der Verbrecher in anthropologischer Beziehung, Stuttgart, 1893, 
Benedikt: Anat. Studien au Verbrecliergehirnen, Wien, 1879; Cent. f. d. med. Wiss., 

1880. 

Charcot; Maladies des vieillards, gouttes et rhumatisme. (Euv. compl., vii., Paris, 
1890. 

Colin: Stiidien liber die angeb. Farbenblindlieit, Breslaii, 1879. 

Cohnheim: Vorlesungen liber allgemeine Patliologie, Berlin, 1882. 

Crocq: L'unite de la diathese et I'lieredite morbide. Rev. de med., 1893. 

Ebstein: Die Fettleibigkeit, Wiesbaden, 1882; Natur imd Behandlung der Giclit, 

Wiesbaden, 1882; Beitr. z. Lehre vender liarnsauren Diathese, Wiesbaden, 1891; 

Die Stellung der Fettleibigkeit, der Giclit iind der Zuckerkranklieit im nosolog. 

System. Deutsch. med Wocli., 1898. 
Fere : Nervenkranklieiten imd ilire Vererbung, Berlin, 1896. 



56 



THE INTRINSIC CAUSES OF DISEASE. 



Le Gendre: L'heredite. Pathol, gen. publ. par Bouchard, i., Paris, 1895. 
Grassmann: Erblichkeit der Psy chosen. Zeitschr. f. Psych., 52 Bd., 1895. 
Haeckel: Antliropogenie, 1891. 

Kisch: Die Fettleibiglveit, Stuttgart, 1888, and Eulenburg's Realencyklop., Art. 
Fettsucht, 1895. 

Kolisch.: Wesen und Behandlung der uratisclien Diathese, Stuttgart, 1895. 
Koller: Erblichkeitsstatistik der Geisteskrankheiten. Arch. f. Psych., 27 Bd., 1895. 
Kurella: Cesare Lombroso und die Naturgeschichte des Verbrechers, Hamburg, 1893. 
Lee: De I'obesite, Paris, 1886. 

Locher-Wild: Ueber Familienanlage und Erbliclilveit, Zurich, 1874. 
Lombroso: Der Verbrecher, i.-iii. (mit Bilderatlas), Hamburg, 1891-1895. 
Lombroso u. Ferrero: Das Weib als Verbrecherin und Piostituirte, Hamburg, 1894. 
V. Noorden- Pathologic des StotJwechsels (Fettsucht, Gicht), Jena, 1893. 
Pfeiffer: Das Wesen der Gicht, Wiesbaden, 1891. 

Schaeffer: Fotale Ohrformen bei Erwachsenen. Arch. f. Anthropol., x\i., 1892. 
Sernojff: Die Lehre Lombroso's. Biol. Centralbl., xvi., 1896. 
Virchow: Descendenz u. Pathologic. Virch. Arch., 103 Bd., 1886. 
Wag-ner: Die Kraukheitsanlage. Deutsch. Arch. f. klin. Med., 23 Bd., 1888. 
Wiedersheim : Der Bau des Menschen, Freiburg, 1893. 
See also § 17. 

§ 17. The origin of diseases attributed to intrinsic causes — that is, 
of diseases in which extrinsic influences are either entirely absent during 
both intra- and extra-uterine life, or are of significance only as a source 
of irritation sufficient to excite into development pathological tendencies 
already present in the body — may be explained in two ways : Either the 
patliological peculiarities of the individual concerned ore inherited from the 
ancestors, or they are develojyed from the seed, i.e., from the individual sexual 
nuclei that have copulated or from the segmentation nucleus resulting from 
their nnion. 

The inheritance of pathological qualities is a fact clearly shown by 
clinical observations, inasmuch as many of the examples of diseases due 
to intrinsic causes which are cited in § 16 also appear as inherital)le 
cliaract eristics in certain families. In some cases these characteristics 
are transmitted from the parents to the children, in other cases the 
grandchild may exhibit pathological peculiarities of the grandparents, 
the parents themselves remaining exempt; finally, in other cases the 
pathological peculiarity may be manifested in individuals of the collat- 
eral branches, as from uncle to nephew. Dwarfishness and giantism are 
pathological peculiarities which frequently characterize certain families. 
Six fingers, cleft-hand and cleft-foot, hare-lip, dextrocardia, birth-marks, 
multiple exostoses, fibromatosis of the nerves, and multiple neurofibro- 
mata may appear in families for many successive generations. 

Congenital haemophilia is also an inheritable condition, which is 
ordinarily transmitted through the daughter to a male grandchild, the 
daughter not showing the disease. There may occur, however, a direct 
transmission of h£emophilia from parents to children. Partial or total 
color-blindness also occurs as an inheritable family disease, especially 
affecting the male members, and like haemophilia is transmitted through 
the female line, which does not suffer, to the male descendants. The 
typical pigment-degeneration of the retina, myopia, deaf -mutism, cer- 
tain forms of progressive muscular atrophy, and polyuria (Weyl) are 
also inheritable. 

According to Gairdner and Garrod, in about ninety per cent of the 
cases of gout there is a family history of the disease. 

Of the pathological conditions of the nervous system many are in- 
heritable ; to these belong especially periodic and circular insanity, 
epilepsy, hysteria, congenital insanity, and to a somewhat less extent 



THE INHERITANCE OF DISEASE. 



57 



melancholia, mania, delnsioual insanity, and alcoholism. Progressive 
paralysis, the deliriums, and the conditions of nervous exhaustion are 
but slightly influenced by heredity (Kraepelin). Hagen estimates the 
number of hereditary insane at 28.9 per cent, Leidesdorf at 25 per cent, 
Tigges at over 40 per cent of all cases, while Forel holds that 69-85 per 
cent may be accounted for by heredity. 

In the most severe forms of hereditary degeneration the pathological 
condition itself is inherited, but more frequently the predisposition to 
disease is alone inherited and the morbid condition itself is developed 
through the action of extrinsic harmful influences upon the central ner- 
vous system. The character of the disease in the descendants may be 
the same as in the ancestors (^identical heredity) . More often the charac- 
ter of the disease is changed (transformMional heredity), not infrequently 
in the sense that the severity of the condition increases from generation 
to generation (degenerative heredity). 

According to Morel, there may apiDcar, for example, in the first gen- 
eration, nervous temperament, moral depravity, excesses ; in the second, a 
tendency to apoplexy, severe neuroses, alcoholism ; in the third, psychi- 
cal disturbances, suicidal tendency, intellectual incapacity; finally, in 
the fourth, congenital idiocy, malformations, and arrests of development. 

The occurrence of inheritable diseases is by no means remarkable ; 
it is a well-known fact that in a family not only the peculiarities of race, 
but also of that particular family are inherited, and that very often the 
characteristic qualities of either parent or of both recur in the children. 
As a hypothesis for the explanation of heredity, it is only necessary to 
assume that the peculiar quality under consideration represents not 
merely a somatic change accidentally acquired during the life of the an- 
cestor, but much rather a quality of the ancestor developed from a con= 
genital aniage. Diseases which in a normal individual arise only un- 
der the influences of some external injurious influence are never in a true 
sense inherited (compare § 19), but only those pathological conditions 
existing in the germ are to be regarded as examples of true inheritance. 
If a certain disease, as, for example, a mental disease or myopia, is the 
product of a special inherited predisijosition plus the effect of injurious 
influences which have acted upon the body during life, only that part 
can be transmitted which has its seat in some peculiar congenital anlage, 
but not that caused by external influences — the acquired condition can- 
not be inherited. 

In direct inheritance — i.e., in that form of inheritance in which 
parental qualities are transmitted to the child — the transmission of nor- 
mal as well as of pathological qualities is possible only when both sexual 
cells, in the condition in which they combine, contain the potentialities 
of the characteristics of both parents, in so far as these characteristics 
are transmissible. The product of the union of the sexual cells — the 
segmentation-cell — must, therefore, contain within itself both the pa- 
ternal and maternal qualities. Since the sexual cells do not represent 
a product of the body developing during the course of life, but are rather 
to be regarded as independent structures, which at an early period of 
development are separated from the other parts of the body (that is, from 
the somatic cells) into special organs, where, protected and nourished by 
the body to which they belong, they lead an independent existence ; the 
only possible explanation for the phenomenon of inheritance is found in 
the hypothesis that the individual sexual cells contain, from the time of 
their origin onward, the potentialities of the same qualities which appear 



58 



THE INTRINSIC CAUSES OF DISEASE. 



in the body in which they dwell. Both the sexual cells and the body 
itself, therefore, inherit in general the same qualities from the ancestors. 
Since in the act of fructification only the nuclei of the sexual cells — that 
is, parts of the same — come to copulation, we are compelled further to 
assume that the nuclei are the bearers of inheritable qualities, and the 
peculiarities of the individual arising from the combination of the sex- 
ual nuclei have their foundation in the organization of the nuclei. 

The appearance in the descendants of normal or pathological char- 
acters belonging to the collateral relatives (uncle, great-aunt, or cousin), 
but which are not present in the parents, is known as collateral inheri- 
tance. This phenomenon is explained by the hypothesis that the sexual 
cells, in their origin, received characteristics which the bodies of the 
parents did not receive, or which, at least, did not undergo development 
and manifest themselves in the parental bodies, whereas in certain rela- 
tives they did become manifest. 

The ai)pearance in an individual of normal or pathological character- 
istics which were wanting in the parents, but were present in the grand- 
parents or great-grandparents, is known as atavistic inheritance. This 
phenomenon is explained by the hypothesis that given characteristics of 
the grandi)arents or great-grandparents were transmitted to the sexual 
cells of the son, or of the son and grandson, without developing in the 
body of the first, while the quality thus remaining latent became again 
manifest in the grandson or great-grandson. 

The attempt has been made to give to the atavistic mode of transmis- 
sion — which is of frequent occurrence and is usually confined to the 
immediate generations of ancestors — a wider significance in pathology. 
Thus it has been proposed to explain the occurrence of many newly aris- 
ing pathological conditions, which appear similar to certain somatic 
qualities possessed by remote animal species in the ancestry of man, as a 
reversion to the type of these ancestors. For example, microcephalus 
and micrencephalus have been explained as a reversion to the ape type ; 
and Lombroso is inclined to regard the homo deUnquens as an atavistic 
phenomenon. There can be no doubt that certain writers have gone too 
far in this respect and have mistaken certain acquired pathological for- 
mations or new germ -variations (compare § 18) for atavistic conditions. 
Aside from the question of reversion to the type of the nearest genera- 
tions of ancestors, atavism plays but an insignificant part in pathology, 
and it can really be employed only in the explanation of pathological 
formations in which the tissues show a certain fluctuation of behavior, 
so that not rarely formations arise which in phylogeny or ontogeny rep- 
resent stages of the then normal conditions. In this category belong, for 
example, the occurrence of certain forms of the ear, supernumerary ribs, 
nipples, or mammary glands, and the development of certain muscles 
which are found in the most closely related mammals. 

It is held by manj^ writers that in indiridual cases, acquired pathological conditions 
may, under certain circumstances, be transmitted to the descendants. Some even affirm 
the possibility^ of hereditary transmission of deformities caused by injury, and regard 
such transmission as proved in certain cases. In suppoi't of their view they believe 
that they can refer to the hereditary transmission of birth-marks, malformations of the 
fingers, myopia, mental diseases, predisposition to tuberculosis, etc., as examples, ac- 
cording to their assumption, of diseases which appeared in the tirst instance as ac- 
quired, and which were then transmitted to the descendants. Further, they hold that 
they can point to observations on animals, of which numerous accounts are found in 
the literature, as giving evidence that injuries may cause deformities which are later 
transmitted to the offspring. 



THE INHERITANCE OF PATHOLOGICAL CONDITIONS. 



59 



An unprejudiced examination, however, of the material collected in support of 
this view shows that observations which establish the hereditary transmission of patholog- 
ical characteristics acquired in the individual do not exist. The alleged proofs are found 
in part to be based upon inaccurate observations, in part upon incorrect inferences 
drawn from accurate observations. For example, the assumption that the occurrence 
of a birth-mark in a child in the same region of the skin as that in which the motlier 
has a scar is a proof of inherited deformity is wholly in the wrong, inasmuch as birth- 
marks and scars represent two entirely different pathological processes. If, among the 
descendants of a man who suffered from some form of mental disease and who showed 
this disease only after a certain age through the perversity of his actions, there appears 
an inheritable disease of the central nervous system, or if we note a similar occurrence 
in the case of myopia, we cannot conclude from such observations that the disease of 
the ancestor was purely an acquired condition. The term acquired, in the biological 
sense, can be applied only to that which in the course of the life of an individual arises 
purely from extrinsic influences, but not to a quality, the anlage of which existed al- 
ready in the germ-cell, although this quality did not become manifest until excited to 
development by extrinsic influences. Should there appear in a family inheritable men- 
tal diseases or hereditary myopia, the first case of such diseases may have already been 
due to some pathological alteration of the germ, although no manifestations of the dis- 
ease occurred until some of the outside influences of life excited it to activity, and so 
rendered possible the recognition of the pathological condition. The particular patho- 
logical condition in this case cannot, therefore, be regarded as a purely acquired disease. 

The observations of BroiDn-Sequard that guinea-pigs, in which epilepsy has been 
experimentally induced, can transmit the condition of epilepsy, have been shown by 
Sommer to be incorrect, in that the condition is not a true epilepsy, but a reflex 
•epilepsy, and is not transmitted. 

Against the occurrence of an inheritance of acquired pathological conditions is the 
simple consideration that the human race, which is exposed to so many injurious influ- 
ences, and whose individual members suffer so frequently from disease and mutilations, 
would very soon arrive at a state of extreme misery and stunted growth and would 
eventually perish were only a small part of the acquired diseases transmitted to the 
descendants. Further, the origin of man and animal forms reproducing through ger- 
minal cells is in itself an argument against the possibility of the transmission of qualities 
acquired by the individual. 

The act of fructification — that is, the first step leading to the production of a new 
individual — is accomplished by the copulation of the sexual nuclei — that is, of the 
nuclei of the ovum and spermatozoon. According to the researches of the last decades, 
there can be no doubt that tliese nuclei are the bearers of tlie hereditary characteristics of 
the parents, Wild that the individuality of the copulating nuclei is inherent in the or- 
ganization of the same. It is impossible to conceive in what manner processes taking 
place in the body cells can produce in the sexual nuclei, which lie within special ceils 
in the sexual glands, such alterations of organization that they shall contain in poten- 
tial form the acquired characteristics of the body and transmit them, after copulation 
has occurred, to the descendants. 

Delage was able to fructify non-nucleated portions of the eggs of echinoderras, 
annelides, and mollusks with spermatozoa (merogony). He regards the union of the 
nucleus of the sj^ermatozoon with tlie protoplasm of the egg as the essential feature of 
fructification. This is not applicable to the ordinary method of fructification, but only 
shows that in exceptional cases the entrance of the spermatozoon into the protoplasm 
of the egg is sufficient for the setting-up of further development, and that the nucleus 
of the spermatozoon entering into the egg without uniting with the nucleus of the lat- 
ter exercises an especial influence upon the protoplasm of the egg. 

Darwin in his time represented tlie view that acquired characteristics could be 
transmitted to the descendants, and endeavored to make such phenomena intelligible 
by the theory that molecules from all the cells of the body contribute to the formation 
of the germ-cells, and that, consequently, alterations of the organism can be trans- 
mitted to the germ -cell. Nevertheless, there occur in the writings of Darwin state- 
ments which not only do not agree with this opinion, but directly contradict it. 

Literature. 

{Inheritance of Pathological Conditions. ) 

Adami : Heredity in Relation to the Development of Morbid States. Ref . Handbook 
of Med. Sc., 1902. 

Bernhard: Familiare Erkrankung d. Centralnervensystems. Virch. Arch., 126 Bd., 
1891. 



60 



THE INTRINSIC CAUSES OF DISEASE. 



Bollinger: Ueber Vererbung von Krankheiten, Stuttgart, 1882. 

Brown- Sequard : Arch, de phys., i., 1868, ii., 1869, iii., 1870, iv., 1872 (giebt an, dass 
kunstlicli erzeugte Epilepsie bei Meerschweinchen auf die Jungen iibergehen 
konne). 

Couvelaire: La d.ysostose cleido-cranienne. J. de phj^s., i., 1899. 
Darwin, C. H. : Die Ehe zwiscben Geschwisterkindern imd ibre Folgen, Leipzig, 
1876. 

Dejerine: L'heredite dans les maladies du systeme nerveiix, Paris, 1886. 
Delage: Etude sur la merogonie. Arcb. de zool. exper., 1899. 

Deutschmann : Vererbung v. erworb. Augenalfectionen. Zebender's kl. Monatsbl., 
xviii., 1880. 

Fischer: Ueber bereditare multiple Exostosenbildung. Dtscb. Zeitschr. f. Cbir., 
xii., 1880. 

Grandidier: Die Hilmopbilie, ii Aufl., 1877. 

Griesinger: Die Patbol. u. Tber. der psycb. Krankheiten, 7 Aufl., 1892. 

Gutzmann: Vererbung v. Spracbstorungen. Deut. med. Wocb., 1898. 

Hagen: Statist. Unters. iiber Geisteskrankbeiten, 1876. Ueber die Verwandtschaft 

des Genies mit dem L'resein. Allg. Zeitsclir. f. Psych., xxxiii. 
Henle: Handbuch der rationellen Patbologie, i., Braunschweig, 1846. 
Herrmann: Die Vererbung v. path. Zustanden beim Pferde. Vortr. f. Tbierarzte, 

viii., 1, 1885. 

Hossli: Gescbicbte und Stammbaum der Bluter von Tenna, Inaug.-Diss., Basel, 1885. 
Lossen (Bluterfamilie) : Deut. Zeitschr. f. Cbir., vii. 
Lucas, P.: Heredite naturelle, Paris, 1850. 

Mayer: Spalthand u. Spaltfuss (durch 4 Generat. vererbt.). Beitr. v. Ziegler, xxiii., 
1898. 

Morel: De l'heredite morbide progressive, Paris, 1867. 

V. Nathusius: Die Vorgange der Vererbung bei den Hausthieren, Berlin, 1891. 
Reinecke: Erblicbkeit der multiplen Wachsthumsexostosen. Beitr. v. Bruns, viii., 
1891. 

Roth: Die Tbatsache der Vererbung, Berlin, 1885. Der gegenwartige Stand der 
Frage der Vererbung erworbener Eigenschaften. Wiener Klinik, 7 H., Wien, 
1890. 

Saury : Etude clin. sur la folic hereditaire, Paris, 1886. 
Sioli: Vererbung von Geisteskrankbeiten. Arcb. f. Psych., xvi., 1885. 
Sommer: Die Brown-Sequard'sche Meerschweinchenepilepsie. Beitr. v. Ziegler, 
XX vii., 1900. 

Thoma : Ueber einige senile Veranderungen des Korpers, Leipzig, 1884. 
Virchow: Gesammelte Abbandlungen, Frankfurt, 1856. Virch. Arch., 103 Bd., 1886. 
Weil: Die bereditare Form des Diabetes insipidus. Virch. Arch., 95 Bd., 1884. 
Zander: 1st die Polydaktylie theromorphe Variefat oder Missbildung? Virch. Arch., 
135 Bd., 1891. 

Ziegler: Konnen erworbene pathologische Eigenschaften vererbt werden u. wie 
entsteben erblicbe Krankheiten u. Missbildungen? Beitr. v. Ziegler, i., 1886; Die 
neuesten Arbeiten liber Vererbungs- u. Abstammungslehre u. ibre Bedeutung f. 
d. Patbolos^ie, ib., iv., 1888. 
See also § 16 and § 18. 

§ 18. As has been explained in § 17, inherited diseases are always such as 
have at the very first developed from intrinsic causes^ that is, from certain 
anlage in the germ-cells ; or at least are diseases in which the predisposition 
thereto is a congenital characteristic. Conversely, the statement ruay be 
made^/ia^ all no7^mal or pathological qualities in the germ-cells are inheritable. 

Conseqnently, the questions as to the primary origin of inherited dis- 
eases are identical with the questions concerning the nature of the causes 
of intrinsic diseases — i.e., concerning the origin of those pathological 
qualities which we regard, when appearing later, as arising spontane- 
ously and dependent upon some congenital anlage. 

The first appearance of new pathological characteristics which are 
inheritable may be dependent upon the fact that as a result of sexual 
procreation — i.e., of the union of two sexual nuclei, oue of which is the 
bearer of the transmissible qualities of the father, the other of those of 
the mother — new variations are constantly arising, so that the child is 



THE INHERITANCE OF PATHOLOGICAL CONDITIONS. 61 

never exactly like one parent ; but, on the other hand, in addition to the 
qualities which the parents offer, it possesses also new qualities. Even 
if we assume that the sexual nuclei at times contain in potential form 
exactly the same characteristics as those of the j)arents, the product re- 
sulting from the copulation of these nuclei would present a certain 
degree of variation. In such a case, however, the differences between 
the children of such parents would be but slight. As a matter of fact, 
the different products of the same parents may show an infinite variety, 
by reason of the fact that the germ-cells themselves contain further a 
mixture of the transmissible characteristics of the paternal and maternal 
ancestors, and that this mixture is never the same in the individual 
germ- cells. 

In accordance with this is the fact that the children of a certain fam- 
ily always present important differences in both physical and mental 
qualities. A marked resemblance occurs only in the case of twins aris- 
ing from one egg — i.e., when the process of development of both chil- 
dren has started from the same act of copulation. 

The embryonal variations resulting from the mixture of two indi- 
vidually different hereditary tendencies can find their expression in 
the most varied qualities of the body and mind of the developing child. 
If these do not deviate in a marked degree from the characteristics which 
the different members of the family show, the conditions are regarded as 
normal and ordinarily receive no especial attention. If, on the con- 
trary, important differences of character are produced, the occurrence 
attracts greater attention; and, according to the value which it has for 
the individual concerned, is regarded at one time as something favor- 
able, at another time as something unfavorable, something pathological. 
When small, weak parents produce children who develop into large and 
strong individuals, or when the intellectual capacity of the children sur- 
passes that of the parents, the occurrence is regarded as favorable. If, 
as actually happens, a genius in any branch of human knowledge or skill 
suddenly appears within a family, without any evidence of an especially 
marked mental development in the ancestors, the phenomenon would 
attract general attention and be regarded as a fortunate event. But if, 
on the other hand, strong parents beget children who are weak or 
physically defective, or if they show a mental development inferior to 
that of their parents, or if they show a complete stunting of a part of 
their mental faculties, the neivly appearing variation is regarded as abnor- 
mal, pathological. 

If we consider the experiences which the pathology of man and ani- 
mals furnishes, the assumption seems fully warranted that of the 
transmissible pathological conditions and predispositions, very many, 
perhaps the majority, are referable to a variation of the germ based 
upon the amphimixis. For example, the group of hereditary i^atho- 
logical conditions and predispositions of the central nervous system, 
hereditary myopia, haemophilia, pigmentation of the retina, and poly- 
dactylism may arise in this manner. If such abnormal characteristics 
show themselves repeatedly in the children of the parents, who are them- 
selves normal and have healthy ancestors, it may be assumed that the 
germ-cells of the parents, though individually normal, have through 
their union given rise to a pathological variation. This hypothesis be- 
comes substantiated when one or both parents produce normal offspring 
through copulation with other individuals. 

Besides the variations which are the lesult of normal sexual repro- 



62 



THE INTRINSIC CAUSES OF DISEASE. 



duction, it is very probable that pathological germ-variations which lead 
to the development of transmissible pathological qualities may also arise 
through the action of injurious influences upon the sexual nuclei or the 
segmentation nucleus ; or else that the process of copulation — that is, 
the union of the sexual nuclei — has been disturbed in some manner. 
The injurious substance may be a body -product, or it may come from 
without, and at the same time also produce its harmful effects upon the 
body. Consequently, in these cases we may speak of the acquiring of a 
transmissihJe imthological characteristic through the action of an extrinsic in- 
jurious influence. This does not mean, however, as has been accepted by 
many, that the tissues of the body, under the influence of extrinsic 
harmful Influences, first suffer changes in themselves, and then transfer 
these changes to the germ -cells. It is to be believed, rather, that the 
harmful influence acts directly upon the sexual nuclei or the segmenta- 
tion-nucleus, producing in these a change of some lind, which later leads 
to a pathological development of the individual developing from the im- 
pregnated egg. It is a matter of no importance, so far as the nature of 
the resulting pathological variation is concerned, whether the somatic 
tissues also suffer changes, or of what nature such changes may be. 

If a transmissible pathological characteristic arises, it may, in case it 
does not affect life or prevent reproduction, actually be transmitted, al- 
though this does not necessarily follow. The chances that a particular 
characteristic will be transmitted are greatest when both parents possess 
the same quality, as, for example, when both parents are affected with 
hereditary deaf -mutism or with near-sightedness. If the characteristic 
is wanting in one parent, there is produced most frequently a new germ- 
variation, in which the pathological characteristic fails entirely to mani- 
fest itself, and in the following generations may completely disappear. 
If several descendants are begotten, the pathological characteristic, in 
case it is not wholly lost, may show itself in only a few of the descend- 
ants, and in these in either a modified or in an aggravated form. Not 
rarely it happens that the characteristic remains latent in one generation 
— that is, is confined to the sexual cells, and appears again in the second 
generation. 

There seems to me to be no doubt that, through the copulation of two sexual 
nuclei possessing different hereditary tendencies, variations may be produced, and that 
among these there may be some which are to be regarded as pathological. It is more 
difficult to answer the question whether, besides these, there are not also transmissible 
variations of a pathological nature, w^hich arise through intluences which affect the 
sexual nuclei or the segmentation-nucleus; and further, if we accept the existence of 
such variations, with w^hat frequency do they occur. Weisinann, according to his most 
recently published statements, holds the opinion that the basis of transmissible varia- 
tions is to be found, not in the amphimixis, but rather in the direct action of external 
intluences upon the sexual nuclei. Starting from the assumiption that the variable 
cells or cell-groups derived from the germ (by him designated as hereditary ijieces or 
determinates) are represented in the germ-plasma by special particles, which are formed 
by the grouping together of a number of life-trophMasts or Mophores (molecular groups 
which represent the smallest units of life), and w^ich he calls determinants or determin- 
ing pieces, he believes that he is warranted in ascribing the transmissible variation 
primarily to the changes produced by external influences in the determinants or group 
of determinants contained within the nuclear chromatin, so that finally the hereditary 
pieces or determinates derived from them also suffer changes. He believes that such 
an influence might be exerted by excessive nourishment of a determinant, causing it ta 
grow more rapidly. For example, he regards it as possible that man}' congenital mal- 
formations (for example, an increase in the number of fingers and toes) can be referred 
to a reduplication of the determinant-groups caused by increased supply of nourish- 
ment. According to Weismann, the amphimixis has only a secondary influence in the 
origin of a permanent variation, in that it mixes in constantly new manner the varia- 



THEORIES OF INHERITANCE. 



tions dependent upon the changes in the determinants, but does not in itself produce 
variations. " Tlie deviations which the determinants suffer through unequar con- 
ditions of nutrition constitute the material out of which, through amphimixis in con- 
nection with selection, the visible individual variations are produced, through whose 
increase and combination new forms arise." 

I agree with Weismann in so far as the assumption that the appearance of a new 
variation of pathological nature is in -part to be referred to changes in tlie determinants 
contained within the sexual nuclei, due to the direct action of extrinsic influences. I 
do not, however, believe that there is sufficient ground for attributing, as does Weis- 
mann, the formation of new separate parts to an over-nourishment of single groups of 
determinants. Such a dependence of the germ-plasma upon the surrounding nutritive 
material seems to me scarcely conceivable, and is opposed to all views hitherto held re- 
garding the nutrition of cells. Not only quantitative but much rather qualitative 
changes of the food-material would appear to be necessary in order to produce changes 
in the organization of the determinants. Further, I hold that the amphimixis has not 
only a secondary but much more a primar}'- significance with regard to the origin of 
pathological variations, in the sense that it itself is able to produce new variations. 
Finally, it seems to me that we cannot at the present wholly set aside the hypothesis 
of Ndgeli, according to which the idioplasm is capable of altering its own condition, 
from within outward, in certain fixed directions and according to certain fixed laws,, 
and thus may produce new characteristics. 



Literature. 

( Theoj^ies of Inheritance. ) 

Ackermann: Mechanismus u. Darwinismus in der Pathologic, Halle, 1884. 
Adami: "JSTew York Medical Journal, June 1, 1901. 

van Bemmelen-. Die Erblichkeit erworbener Eigenschaften. Biol. Centralbl., x,, 
1891. 

Bigelow: Heredity. Reference Handbook of Med. Sciences, 2d ed. 
Bonnet: Die stummelschwanzigen Hunde. Beitr. v. Ziegler, iv., 1888. 
Born: Pflliger's Arch., xxxii. ; Bresl. arztl. Zeitschr., 1884; Arch. f. mikr. Anat., xxiv., 
1885. 

Boveri: Geschlechtl. erzeugter Organismus ohne mlitterl. Eigenschaften. M. nied. 
Woch., 1889. 

Darwin: Das Variiren der Thiere u. Pflanzen, Stuttg., 1873; Die Abstammung des; 

Menschen, Stuttgart, 1873; Ges. kl. Schriften v. Ch. Darwin, her. v. Krause^ 

Leipzig, 1886. Origin of Species; The Descent of Man. 
Delage: La structure du protoplasma et ies theories sur I'heredite, Paris, 1895. 
Eimer : Die Eutstehung der Arten, Bd. i., Jena, 1888. 

Emmery: Gedanken zur Descendenz- u. Vererbungstheorie. Biol. Centralbl., xiii.,,. 
1893. 

Galton : Hereditary Genius, London, 1893. 

Hallervorden : Biologische Interferenz u. Erblichkeit. Virch. Arch., 144 Bd., 1896; 
Hartog-: Grundziige d. Vererbungstheorieen. Biol. Cbl., xviii., 1898. 
Heg-ar : Der Geschlechtstrieb, Stuttgart, 1894. 

Hering: Ueber die individuelle Verschiedenlieit des Farbensinns. Prag, 1885. 

Hertwig, O. : Das Problem d. Befruchtung u. d. Isotropic des Eies, eine Vererbungs- 
theorie, Jena, 1884; Exper. Studien am thierischen Ei vor, wahrend u. nach d. 
Befruclitung, Jena, 1890; Entwickelungsgeschichte, Jena, 1893; Praformatiou- 
oder Epigenese? Zeit- u. Streitfragen der Biologic, i., Jena, 1894. 

His : Unsere Korperform, 1874. 

Israel: Angeborene Spalten der Ohrlappchen. Virch. Arch., 119 Bd., 1890. 
Klaatsch: Das Problem d. Vererbung m. Rlicks. auf d. Pathol. Munch', med. 
Woch., 1898. 

Kolliker: Bedeutung d. Zellkerne f. d. Vorgange d. Vererbung. Zeit. f. wlss. Zool., 
xlii., 1885. 

Minot: Vererbung u. Verjtingung. Biol. Centralb., xv., 1895. (See also Original 
Papers in English.) 

V. Nageli, C: Mechanisch-physiol. Theorie der Abstammungslehre, Munchen, 1884. 
Ortmann: Ueber Keim variation. Biol. Cbl., xviii., 1898. 

V. Rath: Vererbung von Verletzungen. Biol. Centralbl., xiil., 1893; Telogonie, ib.^ 
XV., 1895. 

B-ibot; Die Vererbung, Leipzig, 189''. 



64 THE TRANSMISSION OF INFECTIOUS DISEASES TO THE FOETUS. 



Kohde: Gegenw. Stand d. Frage nach d. Entsteliung u. Vererbuug individ. 

Eigeusch., Jena, 1895. 
Romanes: Die geistige Entwickelung d. Menschen, Leipzig, 1893; Darwinist. Streit- 

t'ragen, 1895. 

Roux: Der Kampf der Tbeile im Organismiis, Leipzig, 1881; Entwickelungsmechanik 
des Embryo, Mlincben, 1885; Die Entwickelungsmechanik der Organismen, Wien. 
1890. 

Sanson: L'beredite normale et patbologique, Paris, 1893. 

Schlatter: Gedankeu iiber die Vererbung. Biol. Centralbl., xvi., 1896. 

Schaffer: Fotale Obrformen u. Erbliclikeit ders. Arch. f. Anthrop., xxi., 1892; Die 

Vererbimg, Berlin, 1898. 
Spencer: Unzulanglichkeit d. natiirl. Ziichtwahl. Biol. Centralbl., 1893, 1894. 
Spitzer: Beitrage zur Descendenzlehre, Leipzig, 1886. 

Waldeyer: Befruchtimg ii. Vererbimg. Verh. D. Naturforscli., Leipzig, 1897. 

Weismann: Aiifsatze iiber Vererbung, Jena, 1892; Das Keimplasma, Jena, 1892; 
AUmacht der Naturzlichtuug, Jena, 1893; Aeiissere Einfiiisse als Entwickelungs- 
reize, Jena, 1894; Neiie Gedanken ziir Vererbuugsfrage, Jena, 1896; Ueber Ger- 
minalselection, Jena, 1896. 

Wiedersheim : Der Bau des Menschen. Freiburg, 1893. 

Wilkens: Vererbungslehre auf Grund thierziicliterischer Erfahrungen. Zeitschr. f. 
Thiermed., 18 Bd., 1891; Vererbung erworbener Eigenschaften. Biol. Centralbl, 
xiii., 1893. 

Wilser: Die Vererbung der geistigen Eigenschaften, Heidelberg, 1892. 

Zieg-ler: Kounen erworbene pathol. Eigenschaften vererbt werden ? Beit. v. Ziegler, 

i., 1886; Arb. lib. Vererbung u. ihre^Bedeut. f. d. Pathologic, ib., iv., 1888. 

See also 16 and 17. 

§ 19. In addition to the pathological conditions already mentioned, 
hereditary transmission appears to occnrin the case of a few infectious 
diseases, particularly syphilis, smallpox, varicella, intermittent and re- 
current fever. At all events, cases are observed in which a child, at 
birth or shortly after, shows symptoms of the same disease from which 
the father or mother had been suffering either at the time of procreation 
or during gestation. Such a i)henomenon is, however, entirely different 
from that already spoken of as a hereditary transmission. 

The infectious diseases are caused by organisms which multiply in the 
body. The transmission of the disease to the child becomes possible 
only when the micro-organisms causing the disease find their way into the 
sexual germ-cells, and then also into the impregnated egg, or else pene- 
trate from the maternal organism into the tissues of the child during its 
intra-uterine development. The latter can occur as long as the child re- 
mains in the uterus, and we must therefore assume that the infecting 
organisms pass through the decidual membranes and the outer coverings 
of the ovum — in the later stages of pregnancy through the placenta — and 
so are transported from the maternal to the foetal organism. It is also 
possible that when cohabitation is continued after pregnancy, the micro- 
organisms, which may enter the vagina with the sperm, may penetrate 
into the uterus and thence into the impregnated egg. 

The transmission of infectious diseases to the foetus is beyond all 
doubt a possible occurrence. In the case of syphilis this may take place 
at the moment of impregnation as well as later during the course of 
intra-uterine development, so that syphilis may be transmitted to the 
child by the father as well as by the mother. In the case of smallpox, 
endocarditis, scarlet fever, many instances of the infection of the foetus 
in liter 0 have been observed ; and from recent observations and experi- 
mental investigations there can be no doubt that anthrax-bacilli, pus- 
cocci, and pneumococci, and under certain conditions also typhoid-bacilli 
and tubercle -bacilli can pass through the placenta to the foetus. This 
can only occasionally occur, when the bacteria gain entrance to the 



THE TRANSMISSION OF INFECTIOUS DISEASES TO THE FCETUS. 65 

Iblood-chauuels of the placenta and are able to multiply there and to 
penetrate into the foetal vessels, an event which is rendered possible 
chiefly by the damage done to the placental tissue by the multiplying 
bacteria, whereby the latter are able to pass through and also to multi- 
ply within the tissues of the placenta. 

^ There are, therefore, both germinative and conceptional, also post= 
conceptional, intra=uterine infections, which constitute a pseudo=forni 
of inheritance, in which the peculiar characteristics of the individual 
are not transferred to the embryo, but instead an organized poison finds 
its way into the germ or into the already developing foetus, where it in- 
creases and produces the same disease as that affecting the parent. 

Only of the transmission of disease from the mother to the foetus in 
utero do we possess a more exact knowledge. Germinative, paternal, 
and maternal transmission is known to occur only in syphilis, the spe- 
cific poison of which is not yet known to us. If syphilis is due, as is 
supposed, to a schizomycete, the specific organism, in cases of germina- 
tive infection, must at the time of the discharge of the sexual cells have 
been present either in the egg or spermatozoon. In the latter case, coin- 
cidently or immediately following impregnation, the micro-organisms 
gain entrance into the egg, and remain there in a living state without act- 
ually hindering the further development of the ovum. It must further 
be assumed that the bacteria during the growth of the foetus pass into 
certain tissues and here later give rise to disease-processes. 

Literature. 

(Transmission of Infectious Diseases to the Foetus.) 

Birch-Hirschfeld : Die Pforten d. placentaren Infection d. Fotus. Beit. v. Ziegler, 
ix., 1891. 

Blumer: Congenital Typhoid. Jour. Amer. Med. Assn., xxxv. 

Charrin et Gley: Rech. sur la transmission hereditaire de rimmunite. Arch, de 

phys., vi., 1894. 
Condorelli : Vaiuolo intrauterine in un f eto, Catania, 1890. 
V. Diiring: Hereditare Syphilis. Eulenb. encyklop. Jahrb., v., 1895 (Lit.). 
Eberth: Gelit der Typhusorganismus auf den Fotus liber? Fortschr. d. Med., vii., 

1889. 

Ehrlich: Ueber Immunitat durch Vererbung und Saugung. Ztschr. f. Hj^g., xii., 
1892. 

Ernst: Intrauterine Typhusinfection einer lebensfahigen Frucht. Beit. v. Ziegler, 
viii., 1890. 

Fing-er: Die Vererbung der Syphilis, Wien, 1898 (Lit.). 
Fournier: L'heredite syphilitique, Paris, 1891. 

Kockel u. Lungwitz: Placentartuberkulose beim Kind. Beit. v. Ziegler, xvi., 1894. 
Latis: Uebergahg des Milzbrandes von der Mutter auf den Fotus. Beit. v. Ziegler, 
X., 1891. 

Iiubarsch: Ueber die intrauterine Uebertragung pathogener Bakterien. Virch. Arch., 
124 Bd., 1891. 

MafEucci: Ueb. d. Verhalten d. Embryo gegen Infection. Centralbl. f. allg. Path., 
v., 1894. 

Malvoz: Transmission interplacentaire des microorganismes. Ann. de I'lnst. Past., 
1888 and 1889. 

Morse : Foetal and Infantile Typhoid. Arch, of Ped., 1900. 

Neumann: Vererbung der Syphilis. Arch. f. Derm., xxiv., 1892. 

Porak: Du passage des substances a travers du placenta. Arch, de med. exp., 1894. 

Sehmorl u. Kockel: Tuberk. der menschl. Placenta. Beit. v. Ziegler, xvi., 1894. 

Straus et Chamberland : Transmission des maladies virul. de la mere au fcetus. 

Arch, de phys. , 1883. 
Wolff: Ueber Vererbung von Infectionskrankheiten. Virch, Arch., 112 Bd., 1888, 



5 



CHAPTER II. 



The Spread and Generalization of Disease Through^ 
out the Organism. Autointoxications and 
Secondary Diseases. 

I. rietastasis and Embolism and Their Significance in the Etiology 
of Lymphogenous and Hsematogenous Diseases. 

§20. The transportation, through the hlood or Jympli-stream, of a disease- 
producing agent, and the production of disease at tlic point of deposit of such 
agent, is termed metastasis. This is one of the most common modes of 
the spread of disease throughout the body. Ordinarily the term metas- 
tasis is applied particularly to those cases in which the transportation of 
a given substance is followed by easily recognizable clinical and anatom- 
ical manifestations of disease, esiDecially those of inflammation or tumor- 
formation, so that we are accustomed to speak of metastatic in flammations 
and metastatic tumors. There is, however, no good reason for not includ- 
ing also under metastasis those cases of transportation of corpuscular 
elements through the lymph or blood stream in which the changes pro- 
duced by the transportation are less striking, and are recognizable on\j 
through a more careful anatomical or microscopical investigation. 

The term metastasis indicates further that the substance deposited has 
arisen from some other known place within the body. If the source of 
the transported material is not known, or at least cannot be definitely 
located, we are accustomed to speak of lymphogenous and haematog= 
enous deposits and diseases. The same designation is also applied to 
deposits of known origin. 

The significance of metastasis is in all cases dependent upon the 
properties of the transported body. Insoluble bland foreign bodies of 
small size may have little effect upon the tisstie ; soluble and chemically 
active substances may, on the other hand, produce important tissue 
changes. Bacteria capable of reproduction may give rise to a disease 
which corresponds in general to that produced at the primary focus of 
infection. Tumor-cells capable of groAvth may develop into a secondary 
tumor. The size of the transported body is of essential importance in 
haematogenous metastasis, in that small bodies may pass all the blood- 
vessels, even the capillaries, while larger ones will be carried only 
through those vessels whose lumen is sufficiently large to admit them. 
When the latter have by anj^ means obtained entrance to the arteries of 
the greater or lesser circulation and are carried along by the blood- 
stream, they will become lodged at those divisions of the vessels where 
the vessel-lumen is too small to admit them, and will thereby more or 
less completely obstruct the vessel. This occurrence is designated by the 
special term embolism ; the body blocking the vessel is called an em= 
bolus or a vessel=plug (Fig. 2, h, c). The effect of embolism is in gen- 
eral the more or less complete obstruction of the vessel, partly through 

66 



METASTASIS AND EMBOLISM. 



67 



the embolus itself, partly through au associated coagulation of the 
blood. As a result of such obstruction there is an interference with the 
circulation, which may vary greatly in different cases, in that behind the 
point of obstruction there may be established either a complete or partial 
comj)ensatory circulation, or in other 
cases such a compensation may be en- 
tirely wanting. When the compensa- 
tion is incomplete or wholly absent, 
the area of tissue suiDplied by the ob- 



structed vessel undergoes 



degeneration 




Fig. 2.— Multiple emboli In the branches of 
the pulmonary artery, after thrombosis of the 
right auricle, a, Arterial branch ; b, embolus ; 
c, embolus with secondary thrombosis. 



or dies. 

Both lymj)hogenous and hsemato- 
genous metastasis usually occur in the 
direction of the normal current, but 
under special conditions a transporta- 
tion in the opposite direction may take 
place — retrograde metastasis. Such 
a change of current in the lymx)h- vessels 
occurs when the normal escape of 

lymph from the region involved is hindered through stoppage of the 
lymphatics, and the lymph is forced to seek other outlets. A similar 
condition may occur in circumscribed areas of the peripheral blood- 
vessels. In this way clots arising in the right heart or in the large 
veins of the body msLj be transported into the peripheral veins ; par- 
ticularly under conditions in which there occur backward waves of 
blood which gradually force the clots back into the smaller veins. 
According to the experimental investigations of Arnold uj)on dogs, 
foreign bodies (wheaten grits), which were too large to pass the capil- 
laries, when introduced into the jugular or crural A^eins, as well as into 
the longitudinal sinus of the dura mater, were carried by retrograde 
metastasis not only into the main trunks, but also into the smallest 
branches of the veins of the liver, kidneys, heart, extremities, dura 
mater, pia mater, and orbit, as well as into the posterior bronchial veins. 

In the case of a defect in the septum of the heart, bodies circulating 
in the blood may pass directly from one side of the heart to the other, 
and thereby give rise to a crossed or paradoxical embolism. 

§ 21. The substances which may be transported in the process of 
metastasis may be conveniently divided into six groups, this classifica- 
tion being based partly upon the origin, partly upon the character of the 
transported body, and partly upon the effects of the metastasis. 

In the first group are placed insoluble lifeless substances composed of 
very small particles, which enter the body from without, and which may 
be designated collectively as dust. The majority of these substances 
enter the body in the respired air, and pass from the lungs into other tis- 
sues. A smaller part may enter the tissues directly through accidental 
or intentional wounds (tattoo). Most frequently these substances are 
particles of soot, coal- and stone-dust, more rarely metal, porcelain, 
tobacco, hair, or other kinds of dust. In tattooing of the skin, soot, cin- 
nabar, and other granular pigments are used. 

The behavior of the tissues of the body towai-d such substances will 
be treated of elsewhere ; it is only necessary to mention here that these 
forms of dust, sometimes in a free state, sometimes enclosed within cells, 
are deposited first in the tissues nearest the point of entrance, further in 
the lymph-vessels and lymphatic glands. In the latter location they 



68 



THE SPREAD OF DISEASE THROUGHOUT THE BODY. 



may remaiu for a life-time ; but in cases of excessive deposit they may 
be carried beyond the lymph-glands, especially in those instances in 
which the glands, because of the great deposit, undergo softening and 
give rise to intiammation and proliferation of the tissues in their neigh- 
borhood. Yery often as a result of such changes the affected glands be- 
come confluent with and break into neighboring veins. This event is es- 
pecially likely to happen at the hilum of the lungs, whereby the contents 
of the gland ultimately, sometimes slowly, at other times more rapidly, 
gain entrance to the vessel-lumen and are carried away hy the blood- 
stream. In the case of the lungs, dust may be deposited directly in the 
vessel-walls and gradually penetrate as far as the intima. Further, the 
particles from a broken-down lymph-gland can again enter the lymph- 
stream, and, if not again arrested by some lymphatic gland, may reach 




Fig. 3- Fat-embolism of the lungs (Flemming's solution, safranin). a. Arteries filled with blackened 
masses of fat ; &, fat-droplets in capillaries ; c, veins ; d, cells in the alveoli. X 100. 

the blood-stream. It is also conceivable that softened lymph-glands may 
break directly into the thoracic duct. 

As numerous experiments have shown, the dust gaining entrance to a 
blood-vessel remains but a very short time in the circulation. Large 
amounts artificially introduced into a vein disappear in a few hours from 
the circulating blood. The greater part collects in the capillaries of the 
liver, spleen, and bone-marrow, partly free and partly within leucocytes, 
in the former case adhering to the surface of the endothelium. After a 
short time the leucocytes containing the dust particles wander out from 
the vessels, so that the dust collects more and more in the tissues, where 
it is held for a long time, partly in wandering-cells, partly in fixed cells, 
and partly free, and under certain conditions may remain here during 
the lifetime of the individual. In the mean time a part is carried in the 
lymphatics to other regions and there deposited, particularly in the por- 
tal and cceliac lymph-glands. According to the researches of Kunkel and 
Siebel, still other cells containing dust -particles may reach the surface of 
the body-cavities, either through the capillaries of the lungs, the paren- 
chyma of the tonsils, and probably also from the lymphoid tissue of the 



METASTASIS AND EMBOLISM, 



69 



intestines, and in this way be discharged externally. From the liver the 
dnst-particles may be passed out in the bile. According to observations 
which may be not infrequently made on inflamed organs, wandering 
leucocytes are able to take up a great number of the particles lying in 
the tissues and transport them from the lungs, intestinal tract, and other 
organs to the surface, and in this way clear the tissues. 

The second group is composed of portions of the body itself, which 
occasionally may be transported through the blood-stream; namely, 
tissue=detritus, parenchymatous cells, and dead, coagulated, and 
broken=up constituents of the blood. Of the elements arising from the 
destruction of tissue, fat=droplets (Fig. 3, a, b, and Fig. 4, a, h) most 
often find their way into the circulation; particularly when through 
trauma or some other pathological process, as, for examijle, haemorrhage, 
the tissues are destroyed. This occurs most frequently in cases of crush- 
ing, destruction, and violent agitation of fat-tissue, as may happen in 
the case of the different panniculi adiposi and the bone-marrow ; but fat 
may also enter the circulating blood through destruction of liver-tissue. 
The parenchymatous cells most frequently entering the circulation are 
liver-cells (Turner, Jiirgens, Klebs, Zenker, von Eecklinghausen, 
Schmorl, Lubarsch), placenta- cells 
(Schmorl, Lubarsch, Leusden), and 
hone-marrow cells (Lubarsch). Or- 
dinarily these are carried into the 
pulmonary arteries and cax)illaries, 
but through retrograde metastasis 
they may be carried into the veins, 
and through paradoxical embolism 
into the arteries and capillaries of 
the systemic circulation. Embo- 
lism of liver-cells and bone-marrow 
giant- cells is caused by traumatic 
and toxic injuries and haemorrhages 
of the affected tissues. Placental- 
cell emboli, in the form of multi- 
nuclear giant- cells, have been ob- 
served especially in puerperal eclampsia, but occur also in the course of 
normal pregnancies (Leusden). In diseased conditions of the intima of 
the heart or blood-vessels, degenerated endothelium, broken-down and degen- 
erated 7nasses of connective tissue of the intima, portions of the valves, and 
material of similar nature may gain entrance to the blood-stream. Frag- 
ments and disintegrated 2)ortions of blood-corpuscles may enter the circula- 
tion from hgemorrhagic foci or may arise within the vessels themselves, 
in the case of degenerative changes produced in the blood through the 
influence of various harmful agents. Coagulated masses of blood enter 
the circulation when a thrombus — i.e., blood coagulated in the vessels 
(see Chapter lY. ) — breaks loose, either in toto or in fragments. 

The fate of the last-named substances is for the chief part dependent 
upon their size and physical properties. All fragments of much greater 
diameter than the lumen of the capillaries become lodged in the bifurca- 
tions of the arteries (Fig. 2, a, b) and usually occlude the same. This 
occurs most frequently in the case of dislodged thrombi or of fragments 
of such ; on the other hand, fat-droplets usually pass into the capillaries, 
where part remain, while others pass through and later become lodged in 
some other place. Since the fat occasionally passes first into the veins 




Fig. 4.— Fat-erabollsm of the kidney (Flemming's 
solution, safranin). a. Glomeruli witb fat in the 
capillaries ; />, fat-droplets in the intertubular capil- 
laries. X 100. 



70 



THE SPREAD OF DISEASE THROUGHOUT THE BODY. 



of the body and thence to the heart, the fat -droplets collect especially in 
the capillaries of the lungs (Fig. 3, h) ; but they may also pass through 
the lungs into the capillaries of the greater circulation, and are then 
found especially in the intertubular and glomerular capillaries of the 
kidneys (Fig. 4, a, b), and also to some extent in the capillaries of the 
brain. Capillary fat- embolism causes a noticeable disturbance of the 
circulation - only when of extensive occurrence; in this case it may lead 
to the production of oedema. Furthermore, the fat disappears in the 
progress of metabolism. 

Parenchymatous cells (in so far as the entrance into the circulation 
of small living cells of the character of lymphoid cells is not concerned) 
become lodged in the capillaries or smaller arteries in the case of arterial 
metastasis. The latter is especially true of liver- eel Is when entering the 
circulation en masse. At the place of lodgment the presence of paren- 
chymatous cells may lead to a heaping-uj) of blood-plates and a hyaline 
coagulation; this is particularly true of liver-cell emboli. The cells 
themselves do not multiply, but they may remain preserved for a certain 
length of time; according to Lubarsch, as long as three weeks. They 
then gradually die, the x^rotoplasm dissolves, the nuclei swell or shrink, 
and finally lose their chromatin. In the case of multinuclear cells the 
dissolution is preceded by a clumping of the nuclei. 

The point of lodgment of loosened thrombi or fragments of thrombi 
depends upon the path which they take, as well as upon their size. 
Since thrombi may be formed in the systemic veins, right heart, and 
pulmonary arteries, as well as in the pulmonary veins, left heart, and 
systemic arteries (see Chapter IV.;, it is possible for embolism to occur 
in any of the arteries of the greater or lesser circulation. Very often 
the emboli iodge at the bifurcation of arteries, forming the so-called 
riding or straddling emboli (Fig. 2, c). Through retrograde metastasis 
emboli may be carried from the vense cav^e or larger veins into the 
smaller veins. Defects in the septum of the heart may lead to the pro- 
duction of a paradoxical embolism. 

Small fragments of thrombi, dead red blood-cells or fragments of 
such, endothelial cells undergoing disintegration or fatty degeneration, 
etc., meet the same fate as dust-particles. They may remain free or be 
taken up by cells ; they are soon removed from the circulation and col- 
lect especially in the spleen, liver, and bone-marrow, where they un- 
dergo further changes and are destroyed. The products resulting from 
the destruction of red blood-cells may persist for a long time in the or- 
gans named, as colored or colorless deposits. 

The third group of substances producing metastases is composed of 
living cells, which, originating from proliferating tissue=foci and hav- 
ing gained entrance to the circulation through direct rupture into the 
blood-vessels, or having entered the lymphatics, are carrried to other or- 
gans. This process may be observed in the case of tumors growing by 
infiltration. The metastasis of living cells from such a tumor leads 
through the proliferation of the transj^orted tumor-cells to the produc- 
tion of metastatic daughter=tumors, which in the case of lymphogenous 
metastasis develop first in the lymph-vessels and lymph-glands, but in 
the case of direct rupture into the blood-vessels arise in that part of the 
vascular system to which the tumor-cells are carried by the blood. The 
metastasis usually occurs in the normal direction of the blood- and lymph- 
streams, but retrograde transportation may also occur, whereby a tumor 
which has brdken into one of the systemic veins may give rise to metas- 



METASTASIS AND EMBOLISM. 



Yl 



tases in the region drained by smaller branches of other systemic veins. 
Eetrograde metastasis is not infreqnently observed in the lymphatic sys- 
tem, when closnre of the efferent lymph- channels has jDrodnced a change 
in the direction of the lymph- current. 

In the fourth group may be placed all those processes characterized 
by the entrance of vegetable or animal parasites into the circulation. 
If under such circumstances these organisms do not find conditions suit- 
able for their development, they are quickly eliminated from the blood- 
stream and destroyed under the influence of metabolic processes. But 
if they are able to reproduce themselves anywhere, they will give rise to 
the production of metastatic foci of infection, which are located partly 
in the vascular system, but also partly extending thence into the neigh- 
boring tissues. The secondary foci in the case of bacterial invasion 
have in general the same character as that of the primary. If an em- 
bolus contains organisms capable of producing tissue-necrosis, inflam- 
mation, and putrid decomposition, there will occur, along with the 
embolism and the accompanying disturbances of circulation, suppuration , 
and sloughing — that is, there will be a repetition of the same processes 
occurring at the original seat of infection. 

As the fifth group of metastatic processes may be classed together 
those cases in which constituents of the human body having under= 
gone solution are transported in the soluble state and again deposited 
in a solid form ; and also those in which extrinsic substances are 
taken up by the body in a soluble form and are then deposited in the 
tissues in a solid state. Of the first class there occurs most frequently 
the resorption of bile-pigments into the circulation within the liver, so 
that these may permeate through the most varied tissues, and at the 
same time give rise to granular or crystalline deposits of MIe -pigment. 
Not infrequently soluble derivatives arising from the destruction of red blood- 
cells in the circulation ai'e deposited in the form of droplets, granules, and 
crystals in the spleen, bone-marrow, liver, and kidneys. Further, soluble 
derivatives of hcemoglobin may be taken up by the lymph and blood from 
hcemorrliagic foci, and deposited in different organs. 

When preparations of silver are, for medicinal purposes, introduced 
into the body through the gastro- intestinal tract for long periods of time, 
there may occur a deposit of fine granules of silver in the connective tis- 
sue of the skin, in the glomeruli, medullary pyramids of the kidneys, 
intima of the large arteries, adventitia of the small arteries, in the neigh- 
borhood of mucous glands, connective tissue of the intestinal villi, in the 
choroid plexus of the cerebral ventricles, and in the serous membranes. 
Tissues showing such a deposit have a grayish -brown color. 

The fact that the epithelial tissues and the brain are not affected 
shows that there is a selective action on the part of the tissues, and that 
this selective action differs essentially from that which is seen in the case 
of a metastatic deposit of corpuscular elements. It may therefore be as- 
sumed that the ehemico-physical character and the functional activity of 
the tissues coming into contact with substances in solution exert a deter- 
mining influence upon the separation and precipitation of such sub- 
stances. 

As a sixth group of metastatic processes may be classed the entrance 
of air into the circulation. If in any manner a large amount of air 
gains entrance to the right heart, an event which occurs especially 
in case of injury to the large veins lying in the neighborhood of the 
thoracic cavity, or more rarely from the opening of a vein, for example, 



THE SPREAD OF DISEASE THROUGHOUT THE BODY. 



of a stomach-veiu, through ulcerative processes, the air miugliug with 
the blood forms a foamy mass, which the cou tractions of the heart are 
scarcely able to drive onward. As a result the left heart receives little 
or no blood, the aortic pressure falls, and the affected individual quickly 
dies. Should the air enter the circulation in small amounts or intermit- 
tently, it may be carried by the blood-stream in form of air-bubbles and 
circulate through the entire body. Larger amounts may lodge for a time 
in the vessels of the major or minor circulation, obstruct their lumpen, 
and cause disturbances of the circulation, which may give rise to func- 
tional disturbances of the brain and resiDiration. If these conditions do 
not cause death, the air is after a time resorbed. 

If the lung-tissue be ruptured through trauma or through violent 
coughing, screaming, or vomiting, etc., air may be forced into the con= 
nective=tissue spaces and lymphatics, and may extend through these 
into all parts of the lungs, pleurse, and the mediastinum, as well as into 
the skin. The conditions thus produced are termed emphysema of the 
skin, of the subcutaneous tissue, of the mediastinum, etc. Under cer- 
tain circumstances the air may spread through a large area of the sub- 
cutaneous lymph-vessels and connective-tissue spaces, whereby the skin 
presents a blown- up appearance and when pressed upon produces a 
crackling sound. 

Arnold, supported by numerous investigations, believes that the lymph -glands 
form a perfect filter for the dust carried to them, and that therefore metastasis of dust 
is possible only through the rupture of a lymph -gland into the blood-sti-eam. In so far 
as the glands do not show too great structural changes, his view appears to me cor- 
rect; but in those cases in which the Ij^mpli-glands undergo softening, as a result of 
being overloaded with dust, portions of necrotic tissue containing dust may pass from 
the glands into the efferent lymphatics. 

As will be shoAvn later (see Inflammation), it is an invariable fact that wherever 
foreign bodies or dead tissue-masses lie in a living tissue, wandering-cells are sure to 
appear; and these, in so far as it is possible, take up into their substance more or less 
of the corpuscular material present. This material is then carried further, especially 
to the lymph-vessels and lymph-glands. It is very probable that a portion of this 
material — in so far as it may be so utilized — serves as nourishment for proliferating tis- 
sue-cells. 

According to Siebel and Kunkel, granules of cinnabar and indigo injected into the 
blood-stream of a frog are quickly taken up b}- leucocytes, and after one to two hours 
no more free granules are to be found in the circulating blood. After twenty-four 
hours the leucocytes containing pigment-granules have disappeared from the circula- 
tion, and lie for the greater part clumped together in the capillaries, the greatest num- 
bers being found in the capillaries of the spleen, liver, bone-marrow, and the lungs, 
while they occur in smaller numbers in the capillaries of the kidneys, and in still smaller 
numbers in the capillaries of the heart-muscle. 

Even after two hours free pigment and cells containing granules are found outside 
of the vessels, and after a few days they have almost wholly disappeared from the ves- 
sels. The granules lie then partly in wandering-cells, partly in fixed cells, as well as 
in the free cells of the splenic pulp (Poufck) and bone-marrow. They may be found 
in these organs for weeks afterward {Hoffmann, Langerhans). In both frogs and dogs 
some of the granule-containing cells find their way into the lumen of the alveoli and 
bronchioles and so pass out of the body. In the liver the pigment-particles for the 
greater part adhere for a short time to the endothelium of the liver-capillaries; another 
part is found in leucocj^tes, which later wander out from the vessels into the tissues. 
Thence they are for the greater part taken up into the lymphatics of the liver and ulti- 
mately reach the lymph-glands. A part of the granules finally pass out with the bile, 
but by what course they reach the bile-vessels is not knowm. In dogs the pigment- 
granules also collect in the tonsils and are carried to the surface through the epithehum 
by the leucocytes which have taken them up. 

According to the investigations of von Kiqjffer, the endothelium of the liver-capil- 
laries (formerly designated as the stellate-cells of Kupffer) possesses phagocytic proper- 
ties, and takes up small particles circulating in the blood-stream. 

According to the observations of Jadassohn (" Pigmentverschleppung aus der 



METASTASIS AND EMBOLISM. 



Y3 



Haut, " Arch.f. Derm. , 24 Bd. , 1892) and Schmorl (" Pigment verschleppung aus der Haut, " 
Centralbl. f. allg. Path., 4Bd., 1893), both normal and pathological pigment may be 
transported from the skin to the lymph-glands — in other words, a pigment-metastasis 
may take place. 

According to Lewin {Arch. f. exp. Path., 40 Bd., 1897), if the outflow of urine from 
the bladder be hindered, small foreign bodies can pass into the kidney -pelves, and 
thence into the urinary tubules, lymph-vessels, and veins, and into the general circula- 
tion. 

Literature. 

{Metastasis of Dust. ) 

Arnold, J. : Staubinhalation u. Staubmetastasen, Leipzig, 1885 ; Die Geschicke des 

eingeathmeten Metallstaubes im Korper. Beitr. v. Ziegler, viii., 1890. 
Gaertner: Ueber die Beziehung des schwarzen Pigments in der Leber, Milz und 

Nieren zu den Kohlenstaubablagerungen. Inaug.-Diss., Strassburg, 1885. 
Hoffmann u. Langerhans: Verbleib des in '^lie Circulation eingefiihrten Zinnobers, 

Virch. Arch., 48 Bd., 1869. 
V. Kupffer: Sternzellen der Leber. Mtinch. med. Woch., 1899. 
Muscatello: Aufsaugungsvermogen d. Peritoneum. Virch. Arch., 142 Bd., 1895. 
Oekonomides : Ueber die chronischenBronchialdrusenaffectionen. Inaug.-Diss., Basel, 

1882. 

Ponfick: Ueber die Schicksale korniger Farbstotfe im Organismus. Virch. Arch., 48 
Bd., 1869. 

V. Recklinghausen: Virch. Arch., 28 Bd. ; Allgem. Pathol, d. Kreislaufs, Stutt- 
gart, 1883. 

Roth: Metastasen von Kalk, Fett Kohlenstaub. Correspbl. f. Schvveizer Aerzte, xiv., 
1884. 

Siebel: Ueber das Scliicksal von Fremdkorpern in der Blutbahn. Virch. Arch., 104 
Bd., 1886. 

Slavjanski: Exper. Beitrage zur Pneumoconiosislehre, ib., 48 Bd., 1869. 
Sticker: Staubkrankheiten. Eulenburg's Realencyklop., xxiii., 1900 (Lit.). 
Sulzer: Durchtritt corpuscul. Gebilde durch d. Zwerchfell. Virch. Arch., 143 Bd., 
1896. 

Weigert: Kohlenstaubmetastase. Fortschr, d. Med., i., 1883. 
Weintraud: Ueber Kohlenstaubmetastase. Inaug.-Diss., Strassburg, 1889. 

(UmboUsm of Fat and of Parenchymatous Cells. ) 

Arnold: Uebertritt v. Knochenmarkzellen ins Blut. Virch. Arch., 140 Bd., 1895. 
Aschoff: Capillare Embolic von riesenkernhaltigen Zellen. Virch. Arch., 134 Bd., 
1893. 

Beneke: Fettembolie. Beitr. v. Ziegler, xxii., 1897. 

Colley: Fettembolie nach gewaltsamer Gelenkbeugung. Zeitschr. f. Chir., 36 Bd., 
1893. 

Ebstein: Lipamie u. Fettembolie bei Diabetes. Virch. Arch., 155 Bd., 1899. 
Flournoy : Contrib. a I'etude de I'embolie graisseuse, Strassburg, 1878. 
Haemig: Fettembolie des Gehirns. Beitr. v. Bruns, 27 Bd., 1900. 
Hamilton: Lipsemia and Fat Embolism. Edinburgh Med. Journal. 1879. 
Hess: Beitr. z. d. Lehre v. d. traumatischen Leberrupturen. Virch. Arch., 121 Bd., 
1890. 

Jiirgens: Fettembolie u. Metastase v. Leberzellen. Tagebl. d. Naturf . -Vers, in Ber- 
lin, 1886. 

Klebs: Multiple Leberzellenthrombose. Beitrage v. Ziegler, iii., 1888. 
Leusden: Puerperale Eklampsie. Virch. Arch., 142 Bd., 1895. 

Lubarsch: Parenchymzellenembolie. Fortschr. d. Med., xi., 1893; Zur Lehre von 

den Geschwillsten u. Infectionskrankheiten, Wiesbaden, 1899. 
Maximow: Parenchymzellenembolie. Virch. Arch., 151 Bd., 1898. 
V. Recklinghausen: Allgem. Pathologic d. Kreislaufs, Stuttgart, 1883. 
Ribbert: Fettembolie. Correspbl. f. Schweizer Aerzte, 1894. 

Schmorl: Embol. Verschleppung v. Lebergewebe. Deut. Arch. f. klin. Med., 42 Bd., 
1888; Organbefunde bei Eklampsie. Cent. f. allg. Path., ii. ; Unters. lib. Puerpe* 
raleklampsie, Leipzig, 1893. 

Scriba: Fettembolie. Deut. Zeitschr. f. Chir., 1879. 

Turner: Hepatic Cells in the Blood. Trans, of the Path. Soc. of London, 1884. 



74 THE SPREAD OF DISEASE THROUGHOUT THE BODY. 



Virchow: Berl. kliu. Woch., 1886, No. 30; Virch. Arch., 5 Bd. ; Ges. Abhandlimgen, 
1856. 

Warthin: Pulmonary Emboli of Liver-cells and Bone-marrow Giant-cells. Med. 
News, 1900. 

Zenker: Scliussverletzung d. Leber mit Verschleppiing v. Lebergewebe. Deut. Arch, 
f. klin. Med., 42 Bd., 1888. 

(Metastasis of Lime-Salts. ) 

Chiari: Verkalkung d. Lunge. Wiener med. Wochenschr., 1878. 
Kiittner: Ueber Kalkmetastase. Virch. Arch., 55 Bd., 1872. 

Xiitten: Ueber patliol. Verkalkungen u. Kalkmetastase in den Nieren. Virch. Arch., 

82 Bd., 1881. 
Prevost: Revue med. de la Suisse rom., 1882. 

Roth.: Metastat. Herz verkalkung. Correspbl. f. Schweizer Aerzte, 1884. 
Virchow : Kalkmetastasen. Virch. Arch., 8 Bd., 1855. 

{Retrograde and Paradoxical Metastasis. ) 

Arnold: Ueber rlicklaufigen Transport. Virch. Arch., 124 Bd., 1891. 

Bonome: Trasporto retrogrado degli emboli e embolia crociata. Arch, per le Sc. 

Med., xiii., 1889. 
Cohn: Klinik der embolisclien Gefasskrankheiten, Berlin, 1860. 
Cohnheim: Vorlesungen liber allgemeine Pathologic, Berlin, 1882. 
Ernst: Rucklauf. Transport in Herz- u. Lebervenen. Virch. Arch., 151 Bd., 1898. 
Hauser: Embol. Verschleppung v. Thromben a. d. r. Herzen in Korperarterien. 

]\runch. med. Woch., 1888. 
Heller: Metastatische Processe in der Leber. Deut. Arch. f. klin. Med., 7 Bd., 1870. 
Litten: Ueber embolische Muskelveranderungen. Virch. Arch., 80 Bd., 1880. 
Lui: Due casi di embolia retrograda. Arch. p. le Sc. Med., xviii., 1894. 
V. Recklinghausen: Venose Embolic u. retrograder Transport. Virch. Arch., 100 

Bd., 1885. 

Ribbert: Retrograder Transport im Venens,ystem. Cbl. f. allg. Path., 1897. 
Schmorl: Leberruptur mit embol. Verschleppung v. Lebergewebe. Deut. Arch. f. 

klin. Med., 42 Bd., 1888. 
Vierth: Rucklaulige Metast. in den Lymphbahnen. Beitr. v. Ziegler, xviii., 1895. 
Vogel: Retrograde Metastase innerh. d. Lymphbahn. Virch. Arch., 125 Bd., 1891. 
Zahn: Paradoxe Embolic. Virch. Arch., 115 Bd., 1889; Geschw^ulstmetastase, ib., 

117 Bd., 1890. 

{Air Umholism.) 

Couty : Etude exper. sur I'entree de Pair dans les veines. Gaz. med. de Paris, 1876. 
Bamsch: Ueber Unterhautemphysem bei Bronchopneumonie. Deut. med. Woch., 
1891. 

Fischer: Lufteintritt in die Venen walirend einer Operation. Deut. Chir., Lief. 18, 
1885. 

Frantzel: Unterhautemphysem bei Erkrank. d. Respirationsapparates. Deut. med. 
AVoch., 1885. 

Hare: Entrance of Air into Veins. Therapeutic Gaz., 1889; Amer. Jour, of jNIed Sc., 
1902. 

Hauer: Erscheinungen im gr. u. kl. Kreislauf bei Luftembolie. Zeit. f. Heilk., xi., 
1890. 

Heller, Mager, u. v. Schrotter: Arterielle Luftembolie. Zeit. f. klin. Med.,32Bd., 

1897. 

Husemann: Luftembolie. Eulenburg's Jahrb., viii., 1899. 

Jlirgensen: Lufteintritt in d. Venen. Deut. Arch. f. klin. Med., 31 Bd. ; Luft im 

Blute, ib., 41 Bd., 1887. 
Panum: Exper. Beitrage zur Lehre von der Embolic. Virch. Arch., 25 Bd., 1862. 
Passet: Ueber Lufteintritt in die Venen. Arbeiten a. d. path. Institut zu Miinchen, 

1886. 

Senn: Entrance of Air, into Veins. Trans. Amer. Surg. Assn., 1885. 



SECONDARY AND GENERAL DISEASES. 



75 



II. Secondary Local and General Diseases. Autointoxication. Diseases 
Caused through Disturbances or Cessation of Gland=Functions. 

§ 22. If through the action of any injurious agent a local tissue- 
change is produced, there occurs first a primary local disease or organ= 

disease, which is accompanied by a disturbance of function of the 
alfecred i)art. If the injurious agent i)asses into the body -juices and 
into the blood without causing noticeable changes at the j)oint of en- 
trance, while within the body it gives rise to local changes, the result- 
ing condition may be designated as a solitary or multiple lymphogenous 
or haematogenous local disease or organ=disease. 

Local diseases may during their entire course remain confined to the 
organ originally affected, yet very frequentlj^ they lead to further sec= 
ondary diseases of organs or to a general disease. 

The first method by which disease-processes spread through the body is 
through metastasis, already described (§§ 20 and 21), by means of which 
there are very frequently formed, not only solitary , but innumerable foci 
of disease throughout the body. Xot infrequently there may occur such 
a generalization of disease by way of the blood and lym]3h-channels (tuber- 
culosis, suppurations, and carcinomatous growths), that the majority of 
the organs will be found to be affected and show corresponding! more 
or less easily recognized functional disttirbances. 

A second method of the spread of disease occurs in those diseases in 
which in the j)rimary foci there are formed toxic products which, taken 
up into the lymph and blood, produce such changes in different organs 
that they must be regarded as intoxications by poisonous substances arising 
fro7n diseased foci. This intoxication is, as shown in § 12, of very com- 
mon occtirrence in the infectious diseases, and leads not only to secondary 
degenerations of organs, but much more to the picture of a more or less 
severe general disease, as shown by general disturbances of metabolism, 
fever, and disturbances of the central nervotis system. 

A third form of the spread of disease -processes throughout the body 
becomes possible by reason of the fact that the integrity and normal 
functional capacity of many organs are to a great measure dependent 
upon the function of other organs; and, further, upon the fact that the 
organism needs, for the i3 reservation of its normal condition, the perfect 
fiTuctional working of its organs, and in the case of many organs cannot , 
permanently dispense with their functions. There is, therefore, a large 
group of local and general diseases which arise as the result of the imperfect 
functional activity of this or that organ. 

A fourth mode of origin of secondary diseases is through autointoxica- 
tion — that is, through a poisoning of the organism by substances ivhich arise 
in the body itself through its own acti city {metabolic poisons), l^he place of 
origin of these substances is in part the intestinal tract {enterogenous 
poisons), and partly the tissues {histogenous iwisons). The cause of the 
poisonous action of these products of metabolism lies partly in the fact 
that they are produced in an increased amount or are retained within the 
body as a residt of disease of certain glands ; partly also that they are 
not transformed to non-poisonotis bodies, as is the case under normal 
conditions. In conditions of disturbed metabolism poisons foreign to 
the normal body may be i3rodticed. 

Disturbance of the function of different glands may cause, in addition to 
autoiutoxication, other manifc'Ji'tions of disease. 



T6 



THE SPREAD OF DISEASE THROUGHOUT THE BODY. 



§ 23. Secondary diseases which arise as the results of patho= 
logical conditions of individual organs occur witL gieat frequency as 
the result of pathological changes in the blood and eircidatortj apparatus. 

The circulatory apparatus and the blood therein contained l)ear cer- 
tain relations to all the body-tissues, and accordingly dim in id ion in 
amount imd jxdhological alterations of the blood, as well as changes of the 
blood-vessels, often give rise to diseased conditions of this or that tissue 
or of the entire organism. If the haemoglobin-content of the blood is 
decreased through a diminution in number of the red blood-cells 
(oligocythpemia), or through a pathological condition of the same, or if 
the haemoglobin through the action of carbon monoxide is rendered in- 
cai)able of taking uj) the oxygen of the air, the body-tissues T^ill no 
longer receive a normal amount of ox^^gen ; consequently there will arise, 
in case the amount of oxygenation falls below a certain point, distm-b- 
ances of nutrition, as the results of which there occur very frequently 
conditions of fatty degeneration, and under certain circumstances death 
through paralysis of the nervous centres. 

Should an artery become narrowed or closed through thrombosis or em- 
bolism, or thicl'cnings of its icalls, as in the case of the arterial disease 
known as arteriosclerosis, there will arise in the region su^jplied by the 
affected vessel a local deficiency of food-sui3ply and oxygen, local as- 
phyxia, and later degenerative processes, which frequently end in the 
death of the specific parenchymatous elements, at times also of the con- 
nective-tissue framework. 

In the brain and spinal cord the vessel -changes lead to ischsemic proc- 
esses of softening, which frequentlj^ result in parah'sis, and not rarely 
in death. In the heart there results a diffuse fatty degeneration or local 
softening of the heart-muscle, giving rise to disturbances of cardiac ac- 
tivity or often even to comi)lete insufficiency. In the kidneys the secret- 
ing glandular j)arenchyma, together with a portion of the connective 
tissue, undergoes necrosis or atrophy ; and the loss of these substances 
gives rise to local or widespread contractions, which, according to their 
origin, are designated as embolic or arteriosclerotic atrophies. 

In the stomach ischsemia of the mucous membranes gives rise to local 
ulcerations; in the liver and muscles to atrophic conditions. Xo tissue 
can withstand the harmful effects of a long-continued anaemia, and con- 
sequently the narrowing and closure of arteries, through the formation 
of clots or through changes in the vessel-walls, play a vei y important 
role in pathology; and are not only the causes of anwmic necrosis (see 
Chapter V. ) and hcemorrhagic infarction (see Chapter lY.), but also of 
numerous progressive atrophies of organs. In the iDathogenesis of the last 
named, arteriosclerosis has an especially important part, since in old 
age it is of very common occurrence, and gives rise to tissue -degenera- 
tions in organs of the most different structure. As evidences of such 
degenerative processes, the majority of the affected organs show later 
areas of scar- tissue, in which the specific parenchyma has disappeared 
while the connective tissue has increased. 

The active particii)ation of the vascular apparatus in all inflamma- 
tory processes (see Chapter TIL), the disturbance of circulation through 
the alteration of the vessel- walls, the shifting and changes of the vascular 
channels which result from the closure of old vessels by proliferation of en- 
dothelium or through thrombosis, as well as from the formation of new 
vessels, make easily comx:)rehensible the fact that in all chronic inflamma- 
tions the specific cells dependent upon a regulated nutrition undergo 



THE RESULTS OF LOCAL ORGANIC DISEASE. YT 

degeneration and are frequently replaced by connective tissue of a lower 
grade than normal. 

A profuse watery discharge from the intestines may deprive the or- 
ganism of water.. If, as a result of stenosis of the oesophagus or pylorus, 
a sufficient amount of food is prevented from entering the intestinal 
tract, or if the stomach and intestine are no longer able to digest the 
food brought to them and to prepare it for assimilation into the body- 
juices, the organism as a whole becomes jDOorer in albumin and fat. 

If the heart is no longer able to force onward with normal strength 
the blood coming to it, there will arise in various organs changes due to 
venous stasis. If the yespiration is hindered or imperfect, the composi- 
tion of the blood suffers changes. Collection of fluid in the thoracic 
cavity causes compression of the lungs; interference with expiration, 
with free inspiration, leads first to distention of the lung and later to 
atrophy. If a part of the lung has been rendered useless by chronic in- 
flammation, the inspiratory enlargement of the thorax afl'ects only that 
portion of the lung which is capable of functionating, and this part be- 
comes over-distended and in consequence finally atrophic. 

Through enlargement of the liver the neighboring organs are com- 
pressed ; diseases of the parenchyma of the liver give rise to disturbances 
of the circulation of blood through the organ, and stasis throughout the 
portal circulation with resulting ascites. 

Hindrance to the outflow of urine from the ureters renders diflicult 
the secretion of the kidneys and leads to their atrophy. The loss of a 
large portion of the parencliyma is followed by increased blood-]3ressure in 
the aorta, increased action of the heart, and hypertrophy of that organ. 

An increased resistance in the pulmonary circulation due to diseased con- 
ditions of the lungs is often followed by dilatation and hypertrophy of 
the right heart. Obstruction to the flow of blood through the aortic opening 
leads to hypertrophy of the left ventricle. Stenosis and insufficiency of 
the mitral valve cause a stasis of blood backward through the lungs to 
the right heart. This may be compensated for through hypertrophy of 
the right ventricle, or may extend farther back into the veins of the sys- 
temic circulation. 

An oblique position of the pelvis leads to curvature of the spine. Stiff- 
ness and immovability of a joint cause atrophy of the muscles moving the 
joint, the atrophy being due to inactivity. 

Diseases of the nervous system may give rise to functional disturbances 
and anatomical changes in any organ of the body — in glands, muscles, 
skin, bones, lung, heart, intestine, etc. These changes are to be referred 
partly to stimulation, partly to inhibition or arrest of nervous impulses, 
and partly to anaesthesia (ansesthetic tissues being especially liable to in- 
jury). Destruction of the large ganglion-cells in the anterior horns of the 
spinal cord leads to the atrophy of the corresponding peripheral nerves 
and muscles. Paralyzed extremities become atrophic. Diseased condi- 
tions in the region of the respiratory and vasomotor centres lead to dis- 
turbances of respiration and circulation. After injury to certain por- 
tions of the medulla oblongata, after concussion of the brain and spinal 
cord, through the presence of tumors in the brain, after psychical affec- 
tions, after poisoning of the nervous system, there is caused under certain 
conditions a rapid withdrawal of the glycogen of the liver into the blood- 
stream and the excretion of sugar in the urine. Stimulation of periph- 
eral nerves may produce abnormal reflex sensations and movements as 
well as circulatory disturbances in other parts of the body. Paralysis 



78 



THE SPREAD OF DISEASE THROUGHOUT THE BODY. 



of both vagi or of their branches, the recurrent hiryngeal nerves, through 
inflammatory changes or through pressure from neighboring lymph- 
ghmds, etc., may be followed by inflammation of the lungs, in that the 
accompanying paralysis of the laryngeal muscles favors the entrance of 
foreign bodies into the lungs during inspiration. 

The so-called trophoneurotic diseases of the tissues are not mentioned above, for 
the reason that the trophic relations of the nervous system to the individual tissues are 
not yet clear, and the views of different authors as to the dependence of the tissues upon 
the nervous system vary greatly. Many authors ascribe to the trophic action of the 
nervous system a far-reaching influence upon the conditions of the tissues, and seek the 
nerves forming the connections Mith the nerve-centres, partly in the motor, secretory, 
sensory, and retlex nerves, as veil as in special trophic nerves. Thus, for example, 
muscular atrophy, glandular atrophy, atroph}" of the bones and joints (in tabes and 
syringomyelia), different pathological conditions of the skin characterized by tliinning, 
exfoliation of the epithelium, loss of hair, intlammations, etc., unilateral tissue- 
atrophies, necroses, also hypertrophic proliferations of muscles, glands, skin, or bones, 
etc., are all referred to affections of the nerves. 

It cannot be doubted that both degenerative and hypertrophic tissue changes and 
inflammations often occur as sequelie to disturbances of innervation, but these most 
probably are not the direct result of the removal or change of nerve-influences affecting 
the tissues, but are rather the results of increased or decreased functional activity of 
the tissue, or of injuries, inflammations, or disturbances of circulation, which have de- 
veloped in connection with the disturbances of innervation — for example, in connection 
with the loss of sensibility. Golz and Eirald, after completel.y destroying the thoracic 
and lumbar portions of the spinal cord of dogs, were able tlirougli great care to pre- 
serve the skin of the animals thus operated upon ; they are, therefore, opposed to the 
theory of the existence of trophic centres and nerves. 



Literature. 

{Trophoneurotic Tissiie-cJianges. ) 

Baldi: Action trophique du systeme nerveux. Arch. ital. de biol., xii., 1889. 
Charcot: Lecons sur les maladies du systeme nerveux. (Euvres completes, i.-iii. 
Dejerine et Leloir: Alter, nerv. dans cert, cas de gangrene. Arch, de phys., 1881. 
Durdufi: Exp. Unters. z. Lehre v. d. trophischeu Nerven. Cbl. f. allg. Path., v., 
1894. 

Frankel: Neurotische Angiosklerose. Wien. klin. Woch., 1896. 
Golz u. Ewald: Hund mit verkurztem Rtickenmark. Pflliger's Arch., 68 Bd., 1896. 
Harbitz : Om de patologisk-anatom. Forundringer af neurotrofisk oprindelse, Chris- 
tiania, 1900. 

Hoclieiiegg: Ueber symmetrische Gangran, Wien, 1886. 

Joseph: Neurotische Hautgangran. Arch. f. Derm., 31 Bd., 1895. 

Kopp : Trophoneurosen der Haut, Wien, 1886. 

Krieg-e: Yasomot. Storun2:en d. Haut bei traumat. Xeurosen. Arch. f. Phvs., 22 Bd., 
1890. 

Leloir: Rech. clin. et anatomo-pathol. sur les affections cutanees d'origine nerveuse, 
Paris, 1882. 

Pitres et Vaillard: Gangrenes massives d'origine nevrotique. Arch, de phvs.. v., 
1885. 

V. RecklingliauserL : Allg. Pathol, des Kreislaufs und der Ernahrung, Stuttgart, 
1883; Multiple Fibrome d. Haut, Berlin, 1882; Akromegalie. Yirch. Arch., 119 
Bd., 1890. 

Rosenbaum : Symmetrische Asphyxie. Eulenburg's Jahrb., ii., 1892. 
Schlesinger : Syringomyelic, Wien, 1895. 

Schwimmer: Die neuropathischen Dermatosen, Leipzig, 1888. 
Springer: Dactylite hypertrophique symetrique. Rev. denied., vii., 1887, 
Weir Mitchell: Des lesions des nerfs et de leur consequences, 1874. 
Ziegler: Ursachen d. pathol. Gewebsneubildungen. Internat. Beitr. Festschr. f. Vir- 
chow, ii., Berlin, 1891. 



§ 24. Autointoxications or self=poisonings may take place in a 
variety of ways. In the first place, jjoisonous products of metaholism of 



AUTOINTOXICATION. 



79 



uornial character and produced iii normal amounts may fail of proper ex- 
cretion, and, being carried over into the juices of the body, may be 
retained in the same. Secondlj^ the 'physiological production of poisonous 
substances may be pathologically increased. Thirdly, it may happen that 
poisonous products of metabolism, which normally are decomposed and 
thereby rendered harmless, may, as a result of a local or general meta- 
bolic disturbance, escape such destruction. Finally, it may also happen 
that, as the result of pathological changes or cessation of the functional 
activity of certain organs, poisonous substances may appear in the Mood and 
also in the urine. According to the place of origin poisons may be classed 
as enterogenous, arising in the intestine, and histogenous, arising in 
the tissues. 

If injurious products arising from the decomposition of albumin are 

retained or formed in excessive amounts in the intestinal canal, they may give 
rise to both local changes and a general intoxication. For example, 
through the action of the bacteria present in the intestines, the sul- 
phuretted hydrogen, arising from the sulphur of albuminous bodies, may 
be formed in such amount as to pass into the blood and impart its char- 
acteristic odor to the breath, and to be found also in the urine. Further, 
those toxins especially which arise from the decomposition of albumin 
through the action of the intestinal bacteria, when taken up into the 
blood are able to produce s^anptoms of poisoning, vomiting, headache, 
vertigo, stupor, acceleration and weakening of cardiac activity, etc. 
This action of toxins is especially marked in those cases in which the 
stomach or pancreas produces little or no enzyme, it being known that 
the enzymes have a neutralizing action upon certain toxins (see § 29). 
It is also probable that the tetany occurring rarely in dilatation of the 
stomach may be due to an autointoxication. 

If the function of the kidneys is disturbed to such a degree that the sub- 
stances convertible into urea are excreted in insufficient quantity, symptoms 
of intoxication msij manifest themselves as the result of the retention of 
these substances. These symptoms are characterized by a condition of 
coma interrupted by convulsions and by disturbances of respiration — the 
symptoms collectively being designated as uraemia. According to von 
Limbeck, the retained substances have a narcotic action, the first effects 
of the narcosis being a dulling of sensibility and insomnia. According 
to Fleischer, the poison leads, through stimulation of the vasomotor cen- 
tre, to a vascular spasm, as a result of which the brain becomes very 
anaemic. It has not yet been determined whether the toxic effects are 
due to a single element or to a mixture of substances. According to 
the investigations of Bohne, it is very probable that the retention of 
chlorides in the organism play the most important part in the production 
of this condition. 

It is very probable that the condition eclampsia, which is associated 
with convulsions, is also to be regarded as a result of changes in the kid- 
neys through which products of metabolism are retained within the or- 
ganism. 

Since many substances are excreted by way of the intestines, it is 
possible that under certain conditions a disturbed function of the intestines 
may render it difficult for the organism to rid itself of poisons and in 
this way lead to an autointoxication. Likewise, an excessive accumida- 
tion of carbonic acid within the blood, through some interference with the- 
exchange of gases in the lungs, may cause symptoms of poisoning. 

When the excretion of bile from the liver is hindered or arrested, through. 



80 



AUTOIXTOXICATION. 



some pathological condition in the bile-passages or in the liver itself, 
the elements of the bile are taken up into the blood, and the condition 
known as cholsemia is produced. Both the biliary salts and bile-pigrnent 
enter the blood, and their presence in the circulation gives rise to gen- 
eral lassitude, depression, mental exhaustion, inclination to sleep, slow- 
ing of the pulse-rate, itching of the skin, and abnormal sensations of 
hearing and taste. The effects upon the heart, muscles, and central ner- 
vous system are ascribed to the bile-salts. These also ])()svo^s a hcemo- 
lytic action ujyon the red blood-cells. According to l]i( k<^l, ammonia- 
salts, leucin, and phenol must also be taken into consideration in the 
explanation of the symptoms. 

If the liver has undergone marked pathological changes, not only does 
the production of the bile as well as that of sugar and urea suffer, but 
certain substances brought to the liver from the intestines and normally 
decomposed by this organ may pass through it unchanged. Many be- 
lie\'e that at least the severe symptoms (conditions of mental excitement, 
delirium, lethargy, coma, and cerebral paralysis) which occur in degen- 
erations of the liver r icterus gra\is) are to be referred in part to the 
presence of such substances in the blood, and base their belief upon the 
fact that under such conditions abnormal substances (ammonium carbo- 
nate) ai:)X)ear in the urine. In degenerations of the pancreas, large 
amounts of dextrose, acetone, and aceto-acetic acid (see § 25) may ap- 
pear in the blood and urine. The two last-named substances have a 
toxic action, and many are disposed to ascril)e such symptoms to a dis- 
turbance of pancreatic function. Finally, after degeneration of the 
thyroid or adrenals (^§26 and 27), pathological symptoms arise which 
possibly may be explained in part by the assumption that, as the result 
of the degeneration of these organs, poisonous products of metabolism 
are no longer destroyed. 

In the constitutional disease known as gout, local deposits of meta- 
bolic products, in the form of urates, give rise to local tissue-degenera- 
tions and inflammations. 

The term autointoxication is not used with the same significance by all writers, 
many of them giving to it a broader meaning than the one given above, and even ap- 
plying the term autointoxication to certain intoxications caused by pathogenic bacteria. 
In justification of such a view it may be said that the poisons in such cases arise for the 
greater part from component elements of the body. At the same time such a widen- 
ing of the significance of tlie term appears to me inexpedient, in that the cause of the 
decomposition lies not in the body itself, but comes from without, so that tlie intoxica- 
tion is the result of a preceding infection. It seems to me, therefore, to be more correct 
to apply the term autointoxication only to those forms of poisoning which are produced 
by products of m.etabolism, either under the influence of the activity of the body-cells 
or through the activity of bacteria constantly present in the intestine. As authoriza- 
tion for including the poisoning by products arising from intestinal decomposition 
among the autointoxications, I draw upon the fact that the intestinal bacilli which 
cause this decomposition are constant inhabitants of the intestine, and, according to the 
investigations of SrJ,otfeI''"f<, are indispensable factors in the processes of nutrition of 
man and tlie liiiiiH-r vertebrates. TJie e/tferor/fnoz/.s fn/fou/toj/rnfionx, which are caused 
])}' these intestinal Ijacteria and whieh occur espf^cially in childhood through retention 
of the intestinal contents (ileusj or in acute digestive disturbances (asthma dyspep- 
ticum), are in their severe forms cJiarac-terized chiefly by disturbance of heart-action, 
small and frequent pulse, cyanosis, coldness of the extremities, sunken expression, and 
lowering of the body temperature. They may owe tljeir origin in part to retention of 
intestinal contents in this or that portion of the intestinal tract, and in part to changes 
in the products of decomposition (toxins and toxalbumins) depending either upon the 
especial character of the material taken into the intestines, or upon a change in the 
virulence of the bacteria, or upon a deficient production of enzymes. It is noi always 
possible in such cases to decide whether other bacteria, foreign to the intestine, are not 



AUTOINTOXICATION : CONSTITUTIONAL DISEASES. 



81 



also concerned in the production of poisons. The appearance of cystin in the urine is 
to be regarded, according to the researches of Baumann and von Udranski, as evidence 
of especial processes of intestinal decomposition resulting in the production of diamins. 

According to the view of Bouchard, autointoxications are caused in particular by 
leucomaius — that is, by the earlier products of retrogressive metamorphosis of albu- 
minous bodies, which normally are further decomposed in the process of intra-organic 
oxidation until they reach the form of urea and are then excreted. 

Chronic diseases whose chief characteristic appears to lie in a changed condition of 
the entire organism are often grouped together as constitutional diseases. Into 
this category Samuel places the permanent anomalies of the blood, lymph-glands, ner- 
vous tissues (neuropathic predisposition), ra'chitis, osteomalacia, multiple exostoses, 
feeble muscular development, relaxed articuiar ligaments, etc. Hoffman (" Lehrbuch der 
Constitutionskrankheiten," Stuttgart, 1894) collects under this term the different forms of 
anaemia, haemorrhagic diathesis, luemoglobinaemia, rachitis, osteomalacia, chronic rheu- 
matism, progressive myositis ossificans, multiple exostoses, lipomatosis, gout, diabetes 
mellitus, diabetes insipidus, and Addison's disease. JSothnag el, in his "Handbook of 
Special Pathology," omits the diseases of the blood from this class, and includes among 
the constitutional diseases only rachitis, osteomalacia, gout, obesity, chronic rheumatism, 
arthritis deformans, diabetes mellitus, and diabetes insipidus. From these examples it 
is clearl}^ evident that the designation constitutional disease is applied to very differ- 
ent conditions. As a matter of fact, the diseases enumerated are not characterized by 
constitutional anomalies ; they represent rather the sequelae of anomalies or diseases of 
certain tissues, so that the use of the term " constitutional disease " finds for the greater 
part no true application. At the most, the designation can still be applied with fitness 
to obesity and gout. 

Literature. 

{Autointoxications. ) 

Albu: Die Autointoxicationen, Berlin, 1895 (Lit.); Jahrb. v. Eulenb., viii., 1898 
(Lit.). 

Baumann: Die aromatischen Verbindungen im Harn u. d. Darmfaulniss. Zeit. f. 

phys. Chem., x., 1886; York. v. Diaminen, sog. Ptomainen im Harn bei Cystinurie, 

\h.\ xiii. , 1889; Alkaptonurie, ib., xv., 1891. 
Bickel: Pathogenese der Choliimie, Wiesbaden, 1900. 
Blum: Autointoxicationen. jMunch. med. Woch., 1900. 
Bohne: Bedeutung d. Retention v. Chloriden. Fortschr. d. Med., xv., 1897. 
Bouchard: Lecons sur les autointoxications, Paris, 1887. 

Bubis: Sperminum-Poehl in chem. u. phvsiol. Beziehung. St. Petersburger med. 
Woch., 1894. 

Charrin: Poisons de I'organisme, Paris, i.-iii., 1893-1897. 

Chatrin et Guinard : Secret int. du rein (has no internal secretion). Arch, de med. 
ex p., 1900. 

Chittenden: Autointoxication. Proc. of the Path. Soc. of Philadelphia, ii., 1899. 
Colosanti: La fonction protectrice du foie. Arch. ital. de biol., xxvi., 1897. 
Ewald: Die Autointoxication. Berl. klin. Woch., 1900. 
Fermi u. Caciani: Aiitointoxication. Cbl. f. Bakt., xix., 1896. 

Fleischer: Beitr. z. exp. Path, der ISTiere. Verh. d. VI. med. Congr., Wiesbaden, 
1887. 

Genzmer u. Volkmann: Septisches u. aseptisches Wundfieber. Klin. Vortr., No. 
121, 1877. 

Goug-et: Insuffisance hepatique et nevrite. Rev. de med., 1897. 

Harz: Die Storungen des Verdauungsapparates als Ursache und Folge anderer 

p]rkrankungen, Berlin, 1898. 
Kobert: Lehrb. der Intoxicationen, Stuttgart, 1893. 

V. Limbeck: Zur Lehre v. d. uramischen Intoxicationen. Arch. f. exp. Path., 30 
Bd., 1892. 

Martius: Pathogenese innerer Krankheiten, i. and ii., Leipzig, 1900. 
Minkowski: Die Storungen d. Leberfunctionen. Ergebn. d. path. An., ii. Jahrg., 
Wiesb., 1897. 

MuUer u. Brieger: Autointoxicationen intestin. Ursprungs. Yerh. d. Congr. f. inn. 
Med., 1898. 

lifesbitt: Res. on Autointoxication. Journ. of Exp. Med., vi., 1899. 
PfeifFer: Yorkommen u. Aetiologie der Tetanic. Cbl. f. allg. Path., vii. 1896 (Lit.). 
Rog-er: Les autointoxications. Path. geo. publ. p. Bouchard, i., 1895. 
6 



82 DISEASES PRODUCED BY DISTURBANCE OF INTERNAL SECRETIONS. 



Schottelius: Bedeutung der Darmbakterien fiir die Erniiliruug. Arch. f. hyg , 34 
Bd., 1898. 

Schwalbe: Vergiftung. Eulenburg's encyklop. Jalirb., iv., 1894. 
Stadelmann : Der Ikterus, Stuttgart, 1891. 

Uschinsky : Intoxication durch Sclnvefelwasserstoll. Zeitschr. f. pbys. Cbem., IT 
Bd., 1892. 

Weintraud: Gastroiutestinale AutoiDtoxication. Ergebn. d. allg. Path., iv., 1897. 
"Wernigk : Ueber die be' uramischen Anf alien auf tret. Veranderungen. Inaug. -Diss. ^ 
Erlangen, 1887. 

Winkler: Zur Lehre v. d. Eklampsie. Yirch. Arch., 154 Bd., 1898. 

§ 25. If a gland produces an internal secretion — that is, if it gives 
to the lymph or the blood certain substances which are necessary for the 
normal performance of the functions of other organs or of the organism 
as a whole — an alteration or total failure of this function will cause 
more or less important disturbances of nutrition, as well as of the func- 
tional activity of other organs and of the entire organism. Such an in- 
ternal secretion is ascribed to the liver, pancreas, thyroid, adrenals, 
thymus, and the sexual glands, yet our knowledge of the nature of these 
secretions is very slight and hypothetical. We are able to infer the in- 
fluence exerted by these glands upon metabolism and the life of the 
organism only from the disturbances which arise when the glands in 
question become diseased. Among the most important of the diseases, 
belonging in this category are diabetes meUitus, thyreoprival eachexiaj 
myxcedema, cretinism, Addison'' s disease, and the functional and anatomical 
changes occurring in the body after castration. In a certain sense it is 
proper to consider in this connection asphyxia, which arises from a fail- 
ure of the lungs to perform property their function, in that through the 
functional activity of the lungs the requisite amount of oxygen is sup- 
plied to the organism. 

Diabetes mellitus is a disease which is characterized especially by 
the presence of large amounts of grape-sugar in the urine (glycosuria), 
accompanied by a great increase in the total amount of urine secreted 
(polyuria), and often also by a pathological increase of acetone and the 
excretion of aceto-acetic acid and /^-oxybutj'ric acid in the urine. At 
the same time grape-sugar and these acids are found in the blood and 
often lead to a diminution of its alkalinity. When the acid-content of 
the blood is high, headache, anxiety, delirium, fainting, and finally a 
condition of loss of consciousness (coma diabeticum) develop, and these 
conditions are probably to be ascribed to an acid-intoxication (Stadel- 
mann, Minkowski, Magnus-Levi). 

The entrance of sugar into the urine may be caused by too great an 
ingestion of sugar, so that part passes into the urine unchanged (ali- 
mentary glj'cosuria). Glycosuria may also follow an injury to certain 
portions of the medulla oblongata (puncture of Bernard) , or as the result 
of disease-processes in the brain (degeneration, epilepsy, mental affec- 
tions, severe psychical disturbances, tumors, parasites), or of certain 
forms of poisoning (carbon monoxide, curare, morphine, strychnine, 
amyl nitrite, nitrobenzole), in which the liver probably gives up its gly- 
cogen into the blood more rapidly than normal, so that a condition of 
hyperglycsemia is produced. 

Finally, glycosuria may be due to an inability on the part of the kid- 
neys to hold back the small amounts of glucose found normally in the 
blood, a phenomenon which may be produced experimentally by the 
administration of phloridzin (von Mering) or of caffeine sulphate 
( Jacob j). 



DISTURBANCE OF PANCREATIC FUNCTION. 



83 



These alimentary, uervous, and toxic glycosurias are, however, to be 
distinguished from the ordinary form of diabetes, in that in the latter the 
cause of the glycosuria is to be sought, not in an increased conveyance 
of sugar into the blood, or in a pathological excretion of the sugar con- 
tained in the blood, but much rather in the fact that the diabetic patient 
is unable to decompose sufficiently the carbohydrates, and especially 
dextrose, while the sugars which turn polarized light to the left (levu- 
lose and inulin) ordinarily can be oxidized either wholly or at least in 
greater amounts than dextrose. In most cases the power to form fats 
from the carbohydrates is also lessened, yet there are cases in which this 
function is unimpaired and the sugars are stored up in the body in the 
form of fat (diabetogenous obesity). 

According to the investigations of von Mering and MiDkowski, which 
have been confirmed by different authors, this loss of power in the or- 
ganism to oxidize the sugars brought into the body or formed normally 
in the body from albumin, or to store them uj) as glycogen or fat, is to 
be ascribed to an insufficiency of pancreatic function. This conclusion 
is drawn chiefly from the fact that after total extirpation of the pancreas 
in dogs, a diabetes of severe character, usually fatal within a few weeks, 
is produced, this being characterized, as is diabetes in the human sub- 
ject, by polyuria, polydipsia, hyperglycsemia, glycosuria, diminution of 
the glycogen of the tissues, also at times by marked destruction of 
albumin, emaciation, excretion of large amounts of acetone, aceto-acetic 
acid, /5-oxybutyric acid, and ammonia, as well as by the occurrence of a 
comatose condition. In support of the view that there is a definite re- 
lation between disturbances of pancreatic function and diabetes, it has 
been found that in certain cases of this disease in man the pancreas has 
exhibited demonstrable changes, of the nature of atrophy or degenera- 
tion. It should, however, be borne in mind that the anatomical investi- 
gation often fails to reveal a pathological condition of the pancreas ; so 
that we are forced to content ourselves with the hypothesis that the 
anatomical changes underlying the functional disturbance of the pan- 
creas are not demonstrable. 

An exact explanation of the causal relations existing between pan- 
creatic disease and diabetes cannot at the present time be given, yet from 
the foregoing experimental researches the hypothesis may be deduced 
that the j^ancreas produces an internal secretion which is of importance 
in the metabolism of glucose, and that if this function is lost the cap- 
acity for the decomposition of glucose is diminished. Likewise, no ex- 
planation can at present be given for the increased destruction of the 
albumins and the accompanying abundant production of i5-oxybutyric 
acid, aceto-acetic acid, and acetone. Since these substances are not al- 
ways found in experimental pancreatic diabetes, their formation probably 
does not stand in direct relation to the excretion of sugar, but is to be 
regarded rather as a complication of diabetes (Minkowski). Their oc- 
currence in diabetes, moreover, is not always constant, and they are 
found in other diseases (intoxications, carcinoma, disturbances of di- 
gestion). 

The occurrence of diabetes after total extirpation of the pancreas is evidence that 
this organ possesses a special function which is of the greatest importance in the nor- 
mal consumption of sugar in the organism. Lepine is of the opinion that there is in the 
blood a glycolytic ferment, which is formed by the pancreas and passed from this or- 
gan into the blood ; and that the cause of the mellituria in diabetic patients and in dogs 
from which the pancreas has been removed is to be sought in a decrease in the amount 



84 DISEASES PRODUCED BY DISTURBANCE OF INTERNAL SECRETIONS. 



of this ferment. According to Miiikoicski, the experiments of Lepine do not offer suffi- 
cient support for this theor}^ At the present time it is impossible to offer a satisfac- 
tory theoiy of the pathogenesis of pancreatic diabetes. 

If only a portion of the pancreas of a dog be removed, no diabetes occurs, or at 
least the excretion of sugar is much less than after total extirpation {Minkoicski). If in 
dogs from which the pancreas has been totally removed a portion of pancreas is trans- 
planted subcutaneousl3% diabetes does not follow (Minkoicski, Hedon), but occurs if the 
transplanted piece be excised. 

According to Minkoicski, there is no direct communication between the secretory 
function of the pancreas and that function of the organ concerned in the metabolism of 
sugar. 

Poisoning with phloridzin produces, according to von Meriug and Minkowski, a 
marked glycosuria in most animals and in man, and the same symptoms as those seen 
in diabetes, may be produced by a continuous administration of the poison. Since in 
this case the cause of the pathological excretion of sugar lies in the kidneys and repre- 
sents a tlushing-out of sugar from the organism, phloridzin diabetes cannot beidentitied 
with the ordinaiy form of diabetes found in man — that is, with pancreatic diabetes. In 
dogs in which diabetes has been produced by the extirpation of the pancreas, phloridzin 
produces an increase in the amount of sugar excreted {Minkowski), 



Literature. 

{Diabetes Mellitus.) 

Arthaud et Butte: Rech. sur la pathogenie du diabete. Arch, de phys., i., 1888. 
Bernard, Claude: Lecons sur le diabete, Paris, 1877, and Berlin, 1878. 
Boceardi: Alterations anat. consec. a I'exportation du pancreas. Arch. ital. de biol., 
xvi., 1891. 

Dominicis: Pathogenie du diabete. Arch, de med. exp., v., 1893. 
Ebstein: Die Zuckerharnruhr, Wiesbaden, 1887. 
Frerichs: Ueber den Diabetes, Berlin, 1884. 

Gaglio: Ueber den Diabetes nach Abtragung des Pankreas. Cbl. f. allg. Path., ii., 
1891. 

Galeotti: Glykosurie und Acetouurie. Cbl. f. allg. Path., iii., 1892. 

Hansemann: Beziehungen d. Pankreas zum Diabetes. Zeit. f. klin. Med., 26 Bd., 

18H4. 

Hedon: Exstirpation du pancreas. Arch, demed. exp., iii., 1891, v., 1898; Pathogenie 
du diabete. Arch, de phys., 1892; Greffe souscutanee du pancreas. Arch, de 
phys., 1892. 

Herter and Wakeman: Adrenalin Glycosuria. Virch. Arch., 1902; Amer. Jour, of 
Med. Sc., Jan., 1903. 

Herzog: Zur Histopathologic des Pankreas beim Diabetes mellitus. Virch. Arch., 
1902. 

Jakobj : Nierendiabetes durch Caffeinsulfosaure. Arch. f. exp. Path., 35 Bd., 1895. 
Kaufmann: Glycemie normale et diabete pancreatique. Arch, de phys., vi., 1895. 
Kiilz : Beitrage zur Pathologic und Therapie des Diabetes mellitus, Marburg, 1874 and 
1875. 

Lannois et Lemoine: Le pancreas dans le diabete. Arch, de med. exper., iii., 1891. 

Lepine: Le ferment glycolytique et la pathogenie du diabete, Paris, 1891 ; S. I'exstirpa- 
tion du pancreas. A. de med. exper.. iii., 1891; Pathogenie de la glycosi\rie, ib., 
iv., 1892; Le diabete et les lesions du pancreas. Rev. de med., xii., 1892; Pa- 
thogenic du diabete, ib., xiv., 1894. 

Lorenz: Unters. iiber Acetonurie. Zeitschr. f. klin. Med., 19 Bd., 1891. 

Liustig": Function des Plexus coeliacus. Beitr. v. Ziegler, vii. , 1890. 

Magnus-Levi : Die Oxybuttersaure u. d. Coma diabet. Arch. f. exp. Path., 42 Bd., 
1899. 

V. Mering": Ueber experimentellen Diabetes. Verhandl. d. V. u. YI. Congr. f. inn. 

MchU Wiesbaden, 1886, 1887; Zeitschr. f. klin. Med., xiv.. 1888, and xvi., 1889. 
V. Mering u. Minkowski: Diabetes mellitus nach Pankreasexstirpation. Arch. f. 

exper. Pathol., 26 Bd., 1890; Zeitschr. f. Biol., 29 Bd., 1892. 
Michael: Diabetes (Cysticercus im IV. Ventrikel). Deut. Arch. f. klin. Med., 44 Bd., 

1889. 

Minkowski: Diabetes nach Pankreasexstirpation. Arch. f. exp. Path., 31 Bd., 1893 
(Lit.). 

Moritz u. Prausnitz: Phloridzindiabetes. Zeitschr. f. Biol., 27 Bd. 
V. Noorden: Pathologic des Stoffwechsels, Berlin, 1893 (Lit.). 



CACHEXIA THYREOPRITA: THYREOPRIVAL TETANY. 



85 



Opie: The Relations of Diabetes 3Iel] 

Med., vol. v., 1901. 
Seeg-en: La glycogenie aiiiinale, Paris, 1890; Der Diabetes me 
Tiroloix: Le diabete paucreatique, Paris, 1892. 



to Lesions of the Pancreas. Journ. of Exp. 

itus, Berlin. 1893. 



§ 26. Cachexia thyreopriva is a peculiar disease caused by deficient 
ortotaUij absent function of the thyroid, resulting either from defective de- 
velopment or from pathological changes in the gland. To Kocher. who 
observed that it followed total extirpation of the thyroid, belongs the 
honor of having discovered the cause of 
this disease. Xnmerous clinical observa- 
tions and experimental researches which 
followed this discovery have confirmed the 
fact that the presence of thyroid tissue is 
essential to the maintenance of the integ- 
rity of the organism, and that the body, 
especially during its period of growth, re- 
quires a thyroid gland capable of function- 
ating normally. It is i^robable that the 
gland produces a substance (thyroiodine) 
which serves a useful puri^ose in the bodily 
metabolism. It is also possible that this 
gland neutralizes or destroys poisonous 
substances circulating in the blood. 

According to ex|)erimental and clinical 
observations, the total extirpation of the 
thyroid gland produces in man and in 
animals, after a \'ery short time, severe 
symptoms, which are characterized espe- 
cially by muscular twitchings, convulsions, 
and parah^sis, so that the condition has 
been called thyreoprival tetany. Young 
animals and carnivora are especially sus- 
ceptible ; dogs die for the greater x^art in 
a short time after total thyroidectomy. 

If the loss of the gland is at first well 
borne, as is the case in man, thv'i-e arise in 
the course of months or years peculiar dis- 
turbances of nutrition, beginning with 
weakness and heaviness of the limbs, feel- 
ing of coldness, often also pain and tran- 
sient swelling of the limbs, with loss of 
mental activity, leading to a cachexia as- 
sociated with aiuTemia, and <"haracterized 

further by pale swellings of the skin, especially of the face (Fig. 5), and 
marked diminution of mental x^owers, together with a loss of muscular 
strength, these symptoms finally terminating in death. The removal 
of the thyroid gland in childhood causes disturbances of growth, the 
increase in length of the bones falling below the normal or ceasing alto- 
gether (Fig. 5). Animals (rabbits and goats) that have had their thy- 
roid glands removed soon after birth do not reach full growth and 
acquire an expression of stupidity. 

In thyreoprival tetany the iDody temperature is increased; in the 
cachexia it is lowered. 

Disturbances of thyroid function, as well as total extiriDation, lead 




Fig. 5. — Thyreoprival cachexia with 
cretin-like disturbance of development, 
in a man twenty-eiarht years oM. arising 
after the tMtal extirpation of th'- tliyri4d 
gland in patient's tenth year: lenetli of 
body 12T cm. iSee Grundler, ha-. citJ 



86 DISEASES PRODUCED BY DISTURBANCE OF INTERNAL SECRETIONS. 



to pathological conditions of the bodj'. Both clinical observations and 
experimental investigations tend to show that the peculiar disease (Fig. 
6) known as myxoedema (Ord) is due to changes in the thyroid. 
Myxoedema is a condition in which the external appearance of the pa- 
tient is suggestive of thyreoprival cachexia, in that the same character- 
istic pale and elastic swellings of the skin of the face (Fig. 6), not pitting 
on pressure with the fingers, are associated with similar jDale and dry 
swellings in other parts of the hody. Further, there is a loss of intel- 
lectual power, which finds expression in an increasing ditficulty in think- 
ing and acting, dulness of the tactile sense, retardation of muscular 
action, and a monotonous nasal voice. Finally, a marked general 
weakness and often also symptoms of actual mental derangement occur, 




Fig. 6.— Myxoedema (case observed Fig. 7.— Myxoedema. The same indivld- 

by Meltzcr).' Age of patient, tliirty- ual (Fig. 6) after three months of treatment 

seven years. with pulverized sheep's thyroid. 



and death follows a gradually increasing cachexia associated with symp- 
toms of ansemia and coma. 

Judging from the clinical and anatomical characteristics presented 
by the patients, cretinism (Fig. 8) — that is, the alterations in the struc- 
ture and functions of the body which characterize this disease — is de- 
pendent upon disturbances of thyroid function. In support of this view 
is the fact that in cretins there is always present some degenerative con- 
dition of the thyroid, the organ being either enlarged and changed in 
structure (goitre) or atrophic. Further, the general aiDpearance of 
cretins (Fig. 8) is similar to that of those individuals who as a result of 
thyroidectomy in early childhood (Fig. 5) have become stunted in de- 
velopment. The~ longitudinal growth of the long bones is more or less 
below that of the normal, while the soft parts are relatively well, devel- 
oped. The individual portions of the body are unequally developed, 
the head is relatively large, the abdomen and neck are thick, the bridge 
of the nose is depressed, while the nose itself is broad and stumpy ; the 
skin is pale, flabby, wrinkled, and puffed, as if cedematously swollen, 
particularly over the face. The mental faculties are always feeble, 
sometimes markedly so. The power of speech and of understanding 



cretinism: function of thyroid. 



8Y 



words may be entirely absent, and only the less marked cases of cretinism 
are capable of performing work of any kind. 

vSince cretinism appears to be an endemic disease in certain regions, 
it lias been assnmed that an unknown local miasm, probably taken into 
the body in the drinking-water, causes degenerative changes in the 
thyroid during the period of development, and injures the organism 
through the disturbance of the function of this gland. There would 
exist, then, a miasm which has the same effect as the operative removal 
of the gland, and if we designate this effect as epidemic cretinism, we may 
apply the term operative cretinism to cachexia thyreopriva. Further, 
myxoedema may be regarded as a form of cretinism, which we may 
designate as sporadic, in contrast to the epidemic form. 



The great importance of the thyroid gland for the general nutrition of tlie organ- 
ism, the cerebral functions, and the development of the bones has been placed beyond 
all doubt by numerous clinical observations and ex- 
perimental investigations. As to the exact mode of 
action of the thyroid, there are, however, different 
opinions. If an animal, after thyroidectomy, is fed 
with the thyroid of some other animal — for instance, 
that of the sheep — the injurious effects usually ob- 
served after removal of the thyroid do not appear 
and will occur only when the feeding is stopped. In 
man the administration of fresh thyroid tissue or of 
thyroid extracts exerts a healing influence on the 
thyreoprival cachexia and myxoedema (Fig. 7); and 
reports have been published of favorable results of 
the same treatment in children suffering from cretin- 
like disturbances of development. 

Goitres (enlarged and hypertrophic thyroids) 
which liave not yet undergone secondary degener- 
ations often diminish greatly in size after the con- 
tinued use of thja'oid tissue for a number of weeks, 
but after the cessation of the treatment soon begin 
to grow again. 

According to Lanz, the extirpation of the thyroid 
in hens causes a diminution in size of the eggs; 
feeding with thyroid causes them to increase in size. 

According to the investigations of Baumann, the 
thyroid constantly contains an iodine substance, 
thyroiodine or iodothyrin, which is present in the 
greatest quantity in old individuals, and in the 
smallest quantity in very young children. Iodo- 
thyrin for the chief part is usually combined in the 
thyroid with an albumin and a globulin body, but it 
may appear in a free form. The normal thyroid is 
able to store up the extremely small amounts of iodine brought into the body in 
vegetable foods or in the drinking-water, and to convert it into the combination men- 
tioned above. Tlie internal administration of preparations of iodine or the treatment of 
wounds with such leads to a greater accumulation of iodine in the tiiyroid. 

According to Baumann, iodothj^rin is the active element of the gland. Its employ- 
ment in the treatment of goitres, myxoedema, and strumiprival cachexia, etc., has the 
same effect as the feeding with fresh thyroid tissue. It would appear that the organ- 
ism requires iodine for its proper maintenance, and that the thyroid supplies it with the 
necessary iodine-combination. In regions where goitres are not commonly found 
(North Germany), the thyroid glands are, on the average, much smaller (fi'om 30-40 
gm. ) and contain more iodine (on the average about 3:^ mgm. instead of 2 mgm.) than in 
regions where goitres are numerous (Switzerland, South Germany). Whether the lack 
of sufiicient iodine in the food and drinking-water is the cause of the hypertrophied 
condition of the thyroid in goitre, or wliether perhaps some lower organism interferes 
with the specific function of the gland, cannot be said at the present time. Among the 
domestic animals having an especially large amount of iodine in the thyroid are 
the sheep, the cow, and the calf, Avhile in hogs the iodine-content of the gland is 
small. 




Fig. 8.— Female cretin, twenty-one 
years old ; body-length 84 cm.; length 
of arm 30cm.; circumference of skull, 
53 cm. (After Virchow.) 



88 DISEASES PRODUCED BY DISTURBANCE OF INTERNAL SECRETIONS. 



Blum regards tlie thyroid as an organ whose function it is to destroy enterotoxins 
arising from the decomposition of albumin in the intestine. 

Anatomical investigations have failed to throw any definite light upon the ques- 
tion of the internal secretion of the thyroid. It has been pioved that the colloid 
produced by the thyroid cells passes into the lymph-vessels. It is probable that 
iodothyrin is contained in this colloid substance. According to Bruns, the diminution 
in the size of the goitre after the administration of thyroid-gland-substance or of thy- 
roiodine may be attributed to the fact that in the hypertrophic gland-tissue of the 
goitre which contains numerous follicles — many of which are entirely destitute of col- 
loid, or contain but little of it, or are imperfectly developed — there occurs an increase 
of colloid-secretion in the fully developed follicles, and at the same time a greater 
abundance of colloid is passed into the lymph-stream, while the imperfectly developed 
follicles, on the other hand, atrophy and disappear. After the administration of active 
thyroid substance for a longer time, some of the secreting follicles also undergo 
atrophy. 

According to the investigations of Rogoicitsch, Stieda, and Hofmeister, the extir- 
pation of the thyroid in rabbits causes enlargement and peculiar changes in the hy- 
pophysis. 

It is possible that Basedoic's disease, which is characterized by a ]:)ulsating and 
highly vascular swelling of the thyroid, projection of the eyeballs from their orbits, 
acceleration of heart action, and great excitability on the part of the patient, is also de- 
pendent upon a diseased condition of the thyroid — namely, a liyinrsecretion {hypertliy- 
reosis). In support of this hj^pothesis is the fact that glands so affected are rich in func- 
tionating gland-tissue; but no positive conclusions can be drawn concerning this point. 



Literature. 

(Cachexia Thyreopriva, Mi/xwdema, Cretinism, and Basedow^ s Disease.) 

Askanazy: Z. Kenntn. d. Morbus Basedowii. Deut. Arch. f. klin. Med., 61 Bd., 1898. 
Baumann: Jod im Tliierkorper. Zeitschr. f. phys. Chem., 21, 22 Bd., 1895-1896; 

Jodothyrin. Munch, med. Woch., 1896. 
Baumann u. Goldmann: Jodothyrin. Miinch. med. Woch., 1896. 
Baumgartner : Zur Kachexia strumipriva. Arch. f. klin. Chir., 31 Bd., 1884. 
Beadles: The Treatment of Mxyoedema and Cretinism. Journ. of Med. Sc., 1893. 
Blum: Schilddriise als entgiftendes Organ. Yirch. Arch., 158 Bd., 1899. 
Blumreich u. Jaeoby: Bedeutung der Schilddriise. Arch. f. d. ges. Phys., 64 Bd., 

1896. 

Bozzi: Unters. lib. die Schilddruse. Beitr. v. Ziegler, xviii., 1895. 
Bruns: Schilddrusenbehandlung d. Kropfes. Beitr. v. Bruns, xvi., 1896. 
Busclian: Myxodem. Eulenburg's Realencyklop., xvi., 1898. 

De Coulon: Tli3''reoidea u. Hypophysis der Kretinen. Yirch. Arch., 147 Bd., 1897. 
Donath: AVirkung d. Schilddriise. Yirch. Arch., 144 Bd., Suppl., 1896. 
Drobnick: Folgen d. Exstirp. d. Schilddruse. Arch. f. exp. Path., 25 Bd., 1888. 
Ehrich.: Z. Kenntn. d. Morbus Basedowii. Beitrage v. Bruns, xxviii., 1900. 
von Eiselsberg: Z, Lehre der Schilddruse. Yirch. Arch., 53 Bd., 1898. 
Ewald: Die Erkrankungen der Schilddruse, Myxodem und Kretinismus, Wien, 1896 
(Lit.). 

Earner: Morbus Basedowii. Yirch. Arch., 143 Bd., 1896. 
Fuhr: Die Exstirpation der Schilddriise. Arch. f. exp. Path., 21 Bd., 1886. 
Gauthin: Fonctions du corps thyroide. Rev. de med., 1900. 
Gley: Etfets de la thyroidectomie. Arch, de phys., iv., 1892; vii.. 1895. 
Grundler: Zur Kachexia strumipriva. Mittheil. a. d. chir. Klinik zu Tlibingen, 1., 
1884. 

Gull: Cretinoid State Supervening in Adult Life in Yv'omen. Trans, of the Clin. Soc, 
London, 1893. 

Hertog-he u. Spiegelberg: Eolle d. Schilddruse bei Hemmung d. Wachsthums, 
Mlinchen, 1900. 

Hofmeister: Physiologic d. Schilddruse. Fortschr. d. Med., 1892; Folgen d. Schild- 

drlisenverlustes. Beitr. v. Bruns, xi., 1894. 
Horsley: Function d. Schilddriise. Internal. Beitr. Festschr. f. Yirchow, i., Berlin, 

1891 (Lit.). 

Jaquet: Schilddriise u. Schilddrlisenpraparate. Corrbl. f. Schweizer Aerzte, 1899. 
Kocher: Kropf exstirpation u. ihre Folgen. Arch. f. klin. Chir., 27 Bd., 1883; Yerhii- 

tuug des Kretinismus. Deut. Zeit. f. Chir., 34 Bd., 1892; Schilddrilsenfunction. 

Correspbl. f. Schweizer Aerzte, 1895. 



ADDISON'S DISEASE. 



89 



Laache: Ueb. Myxodem u. dessen Beliandlung mit Gland, thyr. Deut. med. Wocli., 
1893. 

Lang-endorf; Aeltere u. neuere Ansichten tiber d. Scliilddrlise. Biol. Cbl., ix., 1889. 
Lang-hans: Verand. d. peiiplieren Nerveu bei Kacliexla strumipriva. Virch. Arcli., 
128 Bd , 1892. 

Lannois: De ia cacliexie pachydermique (myxoedeme). Arch, de med. exp., i., 1889. 
Lanz: Zur Schilddrlisenfrage, Leipzig, 1894; Tbyreoidismus. Deut. med. AA'ocli., 1895. 
Leichtenstsm : Heilung v. operat. Myxodem m. Schilddriisenf utterung. Deut. med. 
Woch., 1898. 

Leonhard: Bed. d. Scbilddriise f. d. Wacbstbum. Yircb. Arcb., 149 Bd., 1897. 

Meltzer: Ueber Myxodem, New York. med. Monatsschr., 1894. 

Notkin: Zur Scbilddrilsenpliysiologie. Vircli. Arch., 144 Bd., Suppl., 1896. 

Ord: On Myxoedema. Med.-Cbir. Trans., Ixi. ; and Brit. Med. Journ., 1877. 

Osier: Sporadic Cretinism in America. Trans. Assn. of Amer. Pbys., 1893, vol. viii. 

Oswald: Jodgebalt d. Scbilddriisen. Zeit. f. pbys. Cbem., xxiii., 1897; Function. 

Miincb. med. Wocb., 1899. 
Ponfick: Myxodem u. Akromegalie. Cbl. f. allg. Patb., ix., 1898; Zeit. f. klin. Med., 

38 Bd., 1899. 

de duervain: Verand. d. Centralnervensystems bei Kacbexia tbyreopriva. Yirch. 
Arcb., 133 Bd., 1893. 

Reverdin: Note sur vingt-deux operat. de goitre. Rev. med. de la Suisse rom., 1884. 
E-ogowitsch : Yerand. d. Hypopbyse uacb Entfernung d. Scbilddriise. Beitr. v. 
Ziegier, iv., 1888. 

Roos: Wirkung des Jodotbyrins. Zeitscbr. f. pbys. Cbem., xxii., 1896; xxviii., 
1899. 

Rouxeau: Tb^^roidectomie cbez le lapin. Arcb. de pbys., ix., 1897. 
Sanquirico et Canalis: Sur I'exstirpation du corps thvroi'de. Arcb. ital. de biol., v., 
1884. 

Sclimidt: Der Secretionsvorgang in d. Scbilddriise. Arcb. f. mikr. Anat., 47 Bd., 
1896. 

Schwerdt: Morbus Basedowii. Miincb. med. Wocb., 1898. 

Stewart: The Treatment of Myxcedema by Tbyroid Feeding. Fortscbr. d. Med., 
1894. 

Stieda: Hypopbyse d. Kanincliens nacb Entfernung d. Scbilddriise. Beitr. v. 
Ziegier, vii., 1890. 

Vermehren: Bebandlung d. Myxodems und Kretinismus. Deut. med. Wocb , 1893. 
Vircliow: Kropf. Gescbwulste, iii. ; Kretinismus. Ges. Abbandl., 1856; Woch., 

1887; Kropf kacbexie,. Yirch. Arch., 144 Bd., 1896. 
Weiss: Wucherungen in den peripber. Nerven d. Hundes. Yircb. Arch., 135 Bd., 

1894. 



§ 27. Addison's Disease is a peculiar affection, usually fatal after a 
course of about two years on tlie average, and is very probably to be 
regarded as the result of ^fiincUonal disturbance of the suprarenals. It is 
characterized chiefly by the appearance of a light-yellow-brown to dark- 
brown, diffuse, and spotted pigmentation of the skin (melasma supra- 
renale), which shows itself first in the portions of the skin normallj^ 
exposed, later in other j)arts of the body-surface and in the mucous 
membrane of the mouth. Even at the beginning of the disease, or even 
before the pigmentation of the skin, there occur loss of appetite, nausea, 
pain in the epigastrium, diarrhoea, constipation, and vomiting — all 
symptoms of a disturbed intestinal and gastric function ; later, muscular 
weakness; and finally, nervous symptoms, asthenia, fatigue on slight 
exertion, headache, vertigo, fainting, epileptiform attacks, and coma. 
Occasionally a recognizable increase of the pigment of the skin does not 
occur, and the disease is characterized only by the gastro -intestinal 
symptoms, progressive weakness, and ansemia. 

In about eighty per cent of all typical cases of Addison's disease the 
suprarenals are found to be diseased, in the majority of cases being changed 
into a caseous or fibro-caseous mass. YYith the exception of these 
changes there are no other lesions so constantly characteristic of Addi- 



90 DISEASES PRODUCED BY DISTURBANCE OF INTERNAL SECRETIONS. 



son's disease. There cau scarcely remain any donbt that the disease of 
the suprarenals bears a causal relation to tliis disease ; it may, therefore, 
be designated as a suprarenal cachexia. In what way the loss or change 
of the function of the suprarenal bodies acts injuriously upon the organ- 
ism cannot at present be stated. It is not improbable that the suprarenal 
bodies, like the thyroid, produce a substance which is necessary for the 
preservation of the organism ; or possibly poisonous substances are de- 
stroyed by them. 

The literature of Addiso?i's disease is exceptionally rich, but in spite of the great 
number of clinical and experimental investigations, the pathogenesis of the disease and 
the significance of the adrenals for the human and animal oi-ganism Imxe not yet been 
made clear. Nevertheless, it is certain that a normal functional activity of the adrenals 
is necessary to the integrity of the organism. Tliis is based not only upon clinical ob- 
servations and anatomical investigations in man, but also upon animal experiments. 
For example, the extirpation of the adrenals in dogs, rabbits, cats, and guinea-pigs 
gives rise to a lowering of blood -pressure, muscular weakness, and nervous symptoms, 
paral^'sis, coma, and, if life be sufficiently prolonged, a loss of strength, and, accord- 
ing to Tizzoni, also an abnormal pigmentation of the mucous membranes. The admin- 
istration of adrenal extract causes in animals an increase of blood-pressure, slowing of 
the pulse-rate, increase in the strength of muscle-contractions after nerve-stimulation, 
and a decrease in respirator}- movements. The cause of the increase of blood-pressure 
is regarded by some as the effect of the extract upon the vasomotor centre {Scyrnono- 
icicz), by others as a direct action upon the arterial walls {Schdfer). The contiaction of 
the small vessels has been definitely proved. According to von Ffuilt, the active sub- 
stance is hydro-diox3"pyridiu. which he calls suprarenin. Since the adrenals do not 
show pathological changes in all cases of Addison's disease, the view has been advanced 
by some investigators tliat the disease is dependent upon other local changes, particu- 
larly upon pathological conditions of the sympathetic and the sympathetic ganglia; yet 
the conditions found thus far are not adequate for such an explanation. That in a 
small minority of cases the adrenals appear unchanged cannot (even if all these cases 
had been correctly diagnosed, which is surely not ])]obable) be accepted as valid evi- 
dence against the pathogenic significance of the degenei-ation of the adrenals, inasmuch 
as an apparently normal adrenal may functionate abnormally. 

luflanunatory and degenerative changes in the semihmar ganglia or in other parts 
of the sympathetic, as well as in the intervertebral ganglia have been frequently ob- 
served in Addison's disease. These have been desci'ibed by a number of investigators, 
and may be explained as an extension of inflammation and degeneration from the adre- 
nals to the parts mentioned. To conclude from this that Addison's disease is dependent 
upon a disease of the sj-mpathetic and not of the adrenals, is not sufiicieutly well 
grounded, since the disease of the adrenals actually exists while that of the nerves is 
found onl}' in a minority of cases. 

Manasse found in preparations which, while still retaining the body-heat, were 
placed in solutions of chromic salts and thereby hardened, that the cells ot the adrenal 
stand in closest relations to the veins, reaching out free into the lumen of the veins; 
and that in the vessels, particularly in the veins, thei'e is present a peculiar hyaline 
substance, which is colored brown by the chromic salts in the same manner as are the 
neighboring parenchymatous cells. It is therefore possible that the cells furnish to 
the blood some peculiar substance. It should be stated, further, that this substance is 
found also in the arteries. It cannot be demonstrated in alcoholic preparations. 

As a pathological condition due to the loss of a specific glandular function should 
be classed also those abnormal symptoms in the structure and functions of the body 
resulting from castration — thaf is, the removal from the body of the sexual glands. 
If the ovaries are removed from a woman after the age of puberty, menstruation usu- 
ally ceases at once, but rarely only after some time. Sexual desire and the erethism 
accompanying the sexual act are usually diminished in intensity, but may also be un- 
changed. The remaining portions of the genital apparatus undergo atrophy : this is es- 
peciaUy marked in the case of the uterus. Certain nervous manifestations may follow, 
the most common of which are excitement, with reddening and heat of the skin, espe- 
cially of the face, often associated with attacks of sweating; these symptoms being of 
most frequent occurrence in the period immediately following the castration. The 
disposition remains unchanged or may become more cheerful, especially in those cases 
in which the woman is by the castration relieved of sevei'e pain. At times depression 
or melancholia may follow. If the ovai'ies are removed or destroyed during childliood. 
the body comes to resemble in its build the male tj^pe; the muscles are more strongly 



EFFECTS OF CASTRATIOiS. 



91 



developed, the development of the pelvis is changed, and the breasts do not increase in 
size. 

Castration in an adult male produces no marked change in the build of the body. 
On the other hand, if boys are castrated, the build of the body approaches that of the 
female. There occurs an increased deposit of fat, particularly on the abdomen, while 
the musculature is only feebly developed. The external genitals remain small, the 
prostate is diminished in size, and there is no growth of beard or pubic hair. The 
larynx remains small, and the voice is chikMike. The mental powers are lacking in 
■energy and strength. 

In castrated stags the antlers are not developed ; in cocks the combs, wattles, and 
€ar-lobes do not reach normal development, while the feathers are developed to a 
greater extent [Selllieim). 

According to White, Kirhy, Kummel, Bimns, and others, castration in fully devel- 
oped animals causes a decrease in the size of the prostate; and it is said tha^t in old men 
sulfering from prostatic enlargement, castration may lead to a diminution in size of the 
enlarged prostate. Others {Gzerny, Socin) express a less favorable opinion as to the re- 
sults of castration in such cases. 

In what manner the extirpation of the sexual glands affects the entire body has not 
been determined with certainty. By many authors it is assumed that, as a result of 
castration, the trophic influence exerted upon the tissues by the sexual glands, through 
the nervous system,, is withdrawn. The cessation of the menses may indeed be re- 
garded as due to the withdrawal of nervous stimuli, and the atrophy of the uterus may 
perhaps be dependent upon the same cause; but in general it is more likel}^ that cer- 
tain chemical substances, which exert a certain influence on the functions, growth, and 
development of the body, are formed in the sexual glands. 

According to the investigations of Loeicy and Bicliter, after castration of female 
dogs there occurs a lowering of the oxidation-jDower of the cells of the body and a de- 
crease in the amount of oxygen used by about twenty per cent. The administration of 
dried ovarian substance or of oophorin from the ovaries of the cow or hog causes an in- 
crease of the amount of oxygen consumed even greater than the average observed before 
the castration. Preparations of testicles showed no such influence. In male dogs the 
same conditions prevailed; spermin caused only slight increase in the gaseous inter- 
change, oophorin gave a marked increase (as much as forty-four per cent). 

According to the view of BroiDn-Sequard, all glands produce an especial internal 
secretion, and give to the blood certain substances which are useful to the organism. 
He ascribes to the juice of the generative glands an especial, stimulating, and tonic in- 
fluence upon the organism. According to Poehl, the active substance in the extract of 
the sexual glands is spermin, a base wdiich is found in different glands (thj^roid, pan- 
creas, ovaries, spleen), and which through its catalytic action restores the oxidizing 
power of the blood whenever through various causes it may be lowered, and jyromotes 
in traorga n ic oxida tio n . 

Zoth and Pregel, who have carried out experiments with reference to the effects of 
glycerin extracts of the testicles of animals, report that injections of this extract in- 
crease very markedly the power of muscular contraction. 



Literature. 

{Function of Adrenals and Addison^ s Disease.) 
Abel: Epinephrin. Zeitschr. f. pliys. Chem., 28 Bd., 1899. 

Abelous et Langlois: Fonction des capsules surrenales. Arch, de phys., iv., 1892. 
Addison: On the Constitutional and Local Effects of Disease of the Suprarenal Cap- 
sules, London, 1855. 

Alexander: Die Nebennieren u. ihre Bezieh. z. IS'ervensystem. Beitr. v. Ziegler, xi., 
1891. 

Alezais et Arnaud: Etudes sur la tuberculose des capsules surrenales et ses rapports 

avec la maladie d' Addison. Rev. de med., xi., 1891. 
Averbeck: Die Addison'sche Krankheit, Erlangen, 1869. 

Babes et Kalindero: Un cas de maladie d 'Addison avec lesions des centres nerveux, 
Paris, 1890. 

Burg-er: Die Nebenuieren uud der Morbus Addisonii, Berlin, 1883. 

Chvostek: Storungen d. jSTebennierenfunction. Ergebnisse, iii., 1897. 

Dubois: Toxicite des extraits des caps. surr. Arch, de phys., viii., 1896. 

Pleiner: Veranderungen des sympath. u. cerebrospinal. Nervensy stems bei der Addi- 

son'schen Krankheit. Cbl. f. allg. Path., ii., 1891; Deut. Zeitschr. f. jSTervenheilk,, 

ii., 1892. 



92 DISEASES PRODUCED BY DISTURBANCE OF INTERNAL SECRETIO^S. 



Fiirth: Brenzkatecliin u. aliiil. Subst. d. Nebennieren. Zeit. f. phys. Chem., 29 Bd., 
1899. 

Gerhardt: Blutdruck steigernde Subst. d. Nebennieren. Arch. f. exp. Path., 44 
Bd., 1900. 

Gottlieb: Wirkuiig d. Nebennierenextracto. Arch. f. ex]). Path., 38 Bd. 1896; 43 
Bd., 1899. 

Guinard et Martin: Sue surrenal. Jourii. de phys., i., 1899. 

V. Kahlden: Ueb. Addison 'sche Krankheit. Beitr. v. Ziegler, xi., 1891; C. f. a. P., 
vii., 1896 (Lit.). 

Lewin: Morbus Addisonii. Charite-Ann., x., 1885; xvii., 1892. 

Manasse: Ueber die Bezieh. der Nebeniiieren z. d. Venen. Virch. Arch., 87 Bd., 
1894. 

Mosse: Autointoxication bei Morbus Addisonii. Fortsehr. d. IVled., xv., 1897. 
Oliver: On the Therap. Employ, of the Suprarenal Glands. Brit. Med. Journ., ii., 
1895. 

Philips: Addison's Disease with Simple Atrophy of the Adrenals. Jour, of Exp. 
Med., 1899. 

Rolleston: The Suprarenal Bodies. Brit. Med. Journ., 1895. 

Schafer: Ueber interne Secretion. Wien. med. Bl., 1895. 

Scymonowicz : Function der Nebennieren. Pfliiger's Arch., 64 Bd., 1896. 

Tizzoni: Ueber die Wirkungen der Exstirpation der Nebennieren. Beitr. v. Ziegler, 

vi. , 1889. 

Zander: Functionelle u. genet. Bezieh. d. Nebenn. zum Gehirn. Beitr. v. Ziegler, 

vii. , 1890. 

{Eesults of Castration ; Internal Secretion of Sexual Glands ; Spermin and 

Organ -extract Thera])y. ) 

Alterthum: Folgezust. nach Castration. Beitr. v. Hegar, ii., 1899. 
Brown-Sequard: Exper. dem. la puissance dynamogenique chez I'hommed'un licjuide 

extrait de testicules d'animaux. Arch. d. phys., 1889, 1890, and 1891. 
Bruns: Behandlung d. Prostatahvpertrophie durch Kastratiou. Mittheil. a. d. 

Grenzgeb. d. Med. u. Chir., i., 1896 (Lit.). 
Bubis: Sperminum-Poehl. St. Petersburgcr med. Wochenschr., 1894. 
Buschan: Brown-Sequard'sche Methode. Eulenburg's encyklop. Jahrb., iv., 1894; 

Berlin, 1895. — Organsafttherapie, Eulenburg's Realencyklop., xviii., 1898. 
Curatuto et TaruUi: Intl. de I'ablation des ovaires sur le metabolisme organique. 

Arch. ital. de biol., xxiii., 1895. 
Czerny: Kastration bei Prostatahypertrophie. Deut. med. Woch., 1896. 
Fiirbring-er : Behandl. v. Erkrankungen m. Gewebsfliissigkeiten. Deut. med. Woch., 

1894. 

Gottsclialk: Kastrationsatrophie der Gebarmutter. Arch. f. Gyn., 53 Bd., 1897. 
Heg-ar: Die Kastration der Frauen. Klin. Vortr. v. Volkmann, 1878 ; Der Zusammen- 

haug d. Geschleclitskrankheiten mit nervosen Leiden u. die Kastration bei Ner- 

vosen, 1885; Operative Gynakologie, Wiesbaden, 1897. 
Kiimmel: Operative Heilung der Prostatahypertrophie. Berlin. Klinik, 86, 1895 

(Lit.). 

Liesau: Eintluss der Kastration auf den weibl. Organismus. Inaug.-Diss., Freiburg, 
1896 (Lit.). 

Lilienfeld: Anat. Befund am Genitalapparat nach Kastration. Zeit. f. klin. IMed., 
xxix., 1898 (Lit.). 

Loewy u. Richter: Sexualfunction u. Stolf wechsel. Arch. f. Anat., Suppl., 1899. 
Metschnikoff : Spermatoxine et Antispermatoxine. Ann. de I'lnst. Pasteur, 1900. 
Poehl: Die phys. Chemie uud Grundlagen der Spermintherapie, St. Petersburg, 1898. 
Sellheim: Secundare Geschlechtscharaktere. Beitr. v. Hegar, i., 1898. 
Socin: Kastration u. Prostatahypertrophie. Corr. f. Schweizer Aerzte, 1896. 
Zoth u. Pregl: Wirkung orchitischen Extractes. Ptiuger's Arch., 62 Bd., 1895. 



in. Fever and Its Significance. 

§ 28. When a local organic disease takes on the character of a gen= 
erai disease, or when a disease at its very inception manifests such a 
character, there is seen very frequently a symptom -complex which is 
designated as fever. Particularly in the case of those infectious diseases 



FEVER. 



93 



associated with symptoms of intoxication does the appearance of fever 
during their course phiy an important role. The characteristic sign of 
fever is an increase of bodily temperature ; but accompanying this there 
are other symptoms, especially an increase of the pulse-rate, disturbances in 
the distribution of the blood, changes in the gaseous interchange within the 
lungs, and also changes in the urinary secretion. There is usually also a 
subjective feeling of illness, but this is not a necessary part of the symp- 
tomatology of fever, but an especial effect of an infection associated with 
symptoms of poisoning, the infection occurring at the same time with the 
feverish increase of temperature, or before it, or even after it. 

Observation of the normal body has taught us that, in spite of changes 
of temperature externally and also of changes in other extrinsic condi- 
tions, the body -temperature is maintained at an average height of 37.2- 
37. 4° C. (98. 96-99. 32° F. ). The absolute variation between morning and 
evening is 1-1.5° C. (1.8-2.7° F.), the maximum occurring at evening. 

The elevation of temperature of the body above that of its surround- 
ings is due to the fact that through chemical changes occurring in the or- 
ganism, particularly in the muscles and glands, heat is produced, and to 
such an extent that the temperature of the body may be raised one degree 




PiG. 9.— Temperature-curve of a continued remittent fever, with slowly rising and gradually falling curve 

(typhoid fever). 



Centigrade (1.8° F.) in half an hour. This phenomenon of heat-produc- 
tion is offset by one of heat-disi)ersion, occurring chiefly through the 
skin, lungs, and the excreta. Both heat-production and heat-dispersion 
are under the influence of the nervous system, and through its regula- 
tion of both processes a constant temperature is maintained. 

On exposure to lower temperatures the heat-production is increased 
(chiefly through the agency of the muscles), while heat-dispersion is 
lessened through contraction of the cutaneous vessels and inhibition of 
perspiration. 

On exposure to higher temperatures heat- dispersion is increased 
through increased frequency of respiration, dilatation of the arteries of 
the skin, and increased secretion of sweat. 

In those conditions which we call fever there is a disturbance of the 
regulation of heat-produetion and heat-dispersion, in favor of heat-produc- 
tion, so that the temperature of the body is more or less elevated above tlie 
normal (Figs. 9-11). Elevations of temperature (rectal measurements) 
to 38° C. (100.4° F.) are called hypernormal ; from 38° to 38.5° C. 
(100.4-101.3° F.), light fever; from 38.5 to 39.5° C. (101.3-103.1° F.), 
moderate fever ; 39.5-40.5° C. (103.1-104.9° F.), marked fever; over 
40.5° C. (104.9° F.) (evening temperature), high fever; and over 41° C. 
(105.8° F.), as hyperpyrexia. 

Four periods may be distinguished in fever. The first, which is 



94 EFFECTS OF ORGANIC DISEASES UPON THE ORGANISM AS A WHOLE. 

known as the pyrogenetic or initial stage or stadium incrementi, cor- 
responds to tliat time during which the previously normal temperature 
reaches the average height characteristic of the disease. This period is 
sometimes short (Fig. 10), half an hour to two hours long, and in this 
case is usually accompanied by a chilly sometimes longer (Fig. 9), one to 
several days, and then usually runs its course without a chill, though 
chilly sensations may repeatedly occur. 

In the second period, known as the fastigium, whose duration varies 
according to the disease from a few hours to several weeks, the tempera- 
ture reaches one or &eyenil a one -like highest j^oinfs, between which there 
are more or less marked remissions. 

In the stage of decline of the fever or the defervescence or stadium 
decrementi, the body-temperature returns again to the normal. If this 
takes place through a rapid fall of temperature (Fig. 10), it is called 
crisis ; if slowly, it is termed lysis (Fig. 9). The former is usually ac- 
comx)anied by profuse sweating, and in a few hours, or at most in one 
to one and a half days, the temperature falls tAvo or three degrees, occa- 
sionally as much as five to six degrees Centigrade. In lysis the tempera- 




FiG. 10.— Temperature curve of a con-. FiG. 11.— Temperature-curve of an inter- 

tinued fever with rapidly ascending and mlttent tertian fever (malaria), 

rapidly falling curve (pneumonia). 



ture falls gradually for three to four or more days; the decline may be 
either continuous or intermittent. 

The boundary-line between fastigium and defervescence is not always 
sharply defined, and before the latter sets in there may occur elevations 
of temperature, this phenomenon being called perturbatio critica. If 
between the fastigium and defervescence there occur several days of 
uncertainty with striking fluctuations upward or downward, such period 
is known as the amphibulous stage. Occasionally there may occur a 
short period in which the temperatiu-e is somewhat lowered, but yet re- 
mains high above the normal, to sink after a few days to the normal 
either rapidly or by a gradual decline. 

In the stage of convalescence the temperature returns to the normal 
condition. The heat-regulation is during this time still imj)erfect, so 
that often slight elevations and not infrequently subnormal temperatures 
occur. 

If during the course of a fever the daily variation is slight, so that 
the difference between maximum and minimum is not more than that 
under normal conditions, the fever is called a continuous fever (febris 
continua) (Fig. 10). If the differences are greater, the fever is termed 
subcontinuous (febris subcontinua), remittent fever {fehris remittens) 
(Fig. 9), or intermittent fever {febris intermittens) (Fig. 11). 



FEVER. 



95 



In the last-named, afebrile periods (apyrexia) alternate with periods 
of fever, each paroxysm having an initial period, a fastigium, and a 
defervescence. In the infections disease known as febris recurrens there 
is first a continuous fever, which after a few days falls by crisis ; after 
about a week or so a second rise of temperature occurs, which may be 
followed by a second stage of apyrexia, and this by a third period of fever. 

Many diseases — such as typhoid fever, pneumonia, measles, relapsing 
fever, etc. — are characterized by a typical temperature-curve; others — 
as pleuritis, endocarditis, diphtheria, tuberculosis, phlegmon, etc. — have 
no typical course of fever. 

The elevation of the body=temperature in fever is dependent 
primarily on an increase in heat-production through increase of the chemical 
changes occw^ring in the body. The respiratory interchange of gases — the 
excretion of carbonic acid (Liebermeister, Leyden) and the taking-up of 
oxygen (Zunz, Finkler) — is increased, a proof that the oxidation-proc- 
esses and with these also the heat-production are increased. At the 
same time the excretion of nitrogenous elements in the urine (urea, uric 
acid, creatinin) is increased — on the average about from seventy to one 
hundred per cent, under certain conditions even as much as threefold. 
There is also an increased destruction of the albuminoid substances of the 
body, the albumin of the organs, even in the latent period of the fever 
(I^aunyn). 

The increase of heat-production varies in different fevers, Jbut in gen- 
eral does not reach that degree which can be produced by excessive 
muscle -action and over -feeding with albumin. It is at its highest point 
at the time of the initial chill, in that the violent muscular contractions 
thereby produced may increase the production of heat. 

The second cause of the elevation of the body-temperature is deficient 
heat-dispersion. At the height of the fever the patient as a rule gives 
off more heat than the normal individual, but this dispersion is not suffi- 
cient to offset the excessive heat-production. Heat-production is con- 
stantly increased ; heat-dispersion is irregular. 

In the initial stage the cutaneous vessels are contracted as a result of 
stimulation of the vasomotors, the skin is pale, the heat-dispersion 
slight, under certain conditions even less than normal. 

Chills occur when, through the contraction of the peripheral arteries, 
the supply of blood, and consequently the heat-supply, to the cutaneous 
nerves is suddenly diminished, while in the interior of the body the tem- 
perature is rising. 

In the second stage of fever the skin is often hot and reddened, and 
in certain diseases sweating occurs; but the increased heat- dispersion 
thereby produced is not sufficient to lower the temperature to the nor- 
mal. The increased excitability of the vasomotors or the deficient irri- 
tability of the vaso-dilators (Heidenhain, Kaunyn, Senator) is also 
present during this period, and as a result the skin-temperature, as well 
as the heat-dispersion, varies greatly. The skin is at times pale and 
cold, at other times red and hot, and the hands may be cold while the 
trunk is hot. The centres governing heat-dispersion are therefore act- 
ing faultily. 

In the period of defervescence the relations of heat-dispersion and 
heat-production are changed in favor of the former. The cutaneous ves- 
sels become dilated, the skin gives out a great amount of heat from the 
abundance of blood circulating through it, and when the critical fall of 
the fever occurs there is usually profuse sweating. 



96 EFFECTS OF ORGANIC DISEASES UPON THE ORGANISM AS A WHOLE. 



The cause of fever is not known -ivith certainty, yet this much can be 
said, that fever is most frequently the result of the entrance of a harmful 
agent into the fluids of the body. In many cases this harmful agent arises 
demonstrably from a local focus — for example, from erysipelatous and 
phlegmonous inflammations of the skin. Experimentally, fever may be 
produced by very different procedures — for examj^le, through the infu- 
sion into the vessels of an animal of blood from one of another species, 
through the injection of animal or vegetable substances that a^e begin- 
ning to decompose (Billroth, Weber), and through numerous infections. 
.In man, the infectious diseases, which are regarded as due to specific 
micro-organisms multiplying in the body, are in particular character- 
ized by fever. 

It is probable that the parasites multiplying within the body cause an 
increased tissue-destruction, either directly or through the production of 
unformed ferments, and that at the same time substances are produced 
which act as poisons ujdou the central nervous system. The action of the 
latter may be assumed to be of such a nature that, on one side, the 
activity of the muscles and glands, and consequently the heat-producing 
metabolism, are increased ; while, on the other hand, through the dimin- 
ished and disturbed functions of the nerves governing sweating, as well 
as of the vasomotors, the processes of heat-dispersion fall behind those 
of heat-production. Further, though the organism makes an effort to 
regulate the temperature, it is no longer able to maintain it at the nor- 
mal level, because of the disturbances of the regulating apparatus. 
What share in the increase of body -temperature is due to the direct ac- 
tion of bacteria and of the ferments formed by them, or what share is 
due to the increase of metabolism, through the stimulation of the nerves 
as well as by disturbance of heat- dispersion, cannot at present be deter- 
mined. It is, however, certain that the factors vary in different cases. 
That under certain conditions, changes in the nervous system without 
contamination of the tissue-juices are in themselves sufficient to cause a 
feverish increase of temperature, is shown by the fact that fever may 
occur in epileptic attacks, in the periods of excitation occurring in the 
course of progressive paralysis, after severe frights, after the passage of 
a catheter into the bladder, etc. According to the investigations of 
Eichet, Aronsohn, and Sachs, a marked increase in body-temperature 
with increase of the respiratory interchanges of gases and increased ex- 
cretion of nitrogen (Aronsohn and Sachs) may be produced in animals 
by a puncture which passes through the cerebral cortex and strikes the 
corpus striatum. The same phenomenon may be produced also by elec- 
trical stimulation (Aronsohn, Sachs) of the same portion of the brain. 
^Nevertheless, fevers dependent upon nervous disturbance are rare, and 
are overshadowed in importance by those caused by infection. 

The rise of temperature in fever is usually accompanied by an in= 
crease in the frequency of the pulse=rate ; but in some cases this effect 
of the elevation of temperature may be so greatly modified through 
stimulation of the vagus — as, for example, in basilar meningitis — that 
the pulse-rate may be lowered. The pulse is at one time full and bound- 
ing, at another time small because of weakened contractions of the heart. 

The impairment of the contractions of the heart-muscle is dependent 
partly upon the constant high temperature, partly upon poisonous sub- 
stances, which are produced by the morbid processes peculiar to the es- 
pecial disease, and which exert a harmful influence upon the muscle- 
substance of the heart or upon the nervous system. 



FEVER. 



97 



lu diseases accompanied by fever there is usually a marked sensation 
of illness with a heavy feeling in the head. In severe fevers there occnr 
clouding of consciousness, symptoms of excitation and depression, hal- 
lucinations, delirium, apathy, involuntary evacuations, tremors of the 
hands, convulsions (in children), etc. The muscles of the body become 
weak and not infrequently painful. Digestion is decidedly impaired; 
the appetite for food is slight, but on the contrary there is great thirst ; 
the mouth is dry. There is an increased frequency of respiration ; after 
the appearance of muscular weakness the respiratory movements are 
superficial. The excretion of urine is usually diminished ; the amount 
of urea in the urine is increased, while that of sodium chloride is dimin- 
ished. 

In prolonged fevers there is marked wasting of the body, in that a 
large portion of the albuminous material and fat of the body is de- 
stroyed. 

To what extent these symptoms in individual cases are dependent 
upon the increase of temperature or to what extent upon the damage to 
the organism caused by the specific morbid process, it is difficult to say, 
but the marked effects upon the nervous system must for the greater 
part be regarded as a result of the infection and intoxication. 

Death results most often from cardiac insufficiency, but it may be 
brought about also by the severity of the infection — that is, by the 
changes in the body -fluids (through their influence upon the nervous 
system), by the wasting of the strength, as well as by an excessive ele- 
vation of temperature to 43°, 44°, or 45° C. (109.4°, 111.2°, and 113° 
F.). It should, however, be remarked that under certain conditions very 
high temperatures may be borne for a length of time without fatal re- 
sults, and that the death following very high temperatures cannot be 
ascribed to the abnormal temperature alone, but is rather to be regarded 
in part or wholly as the result of the infection (see § 3). 

The questions coucerning the nature of fever, which Galen designated as Color 
prceter naturam, have been much advanced during the last decades by numerous clin- 
ical and experimental investigations. From these have learned of the associated 
disturbances of metabolism, the increased consumption of oxygen, the increased excre- 
tion of nitrogen and carbon compounds, as well as of the disturbances of the heat-dis- 
persion. If we, in spite of this knowledge, do not yet possess a full understanding of 
all the morbid processes which in a given case may cause fever, we may attribute this 
to the fact that the causa efficiens of fever is not a single entity, but may be one of 
many different factors, and that the feverish elevation of the body-temperature does 
not always occur in exactly the same manner. The increase of the tissue-changes and 
oxidation-processes witliin the body is not always brought about in the same way. 
Further, tlie disturbance of heat-dispersion through radiation from the skin and the 
evaporation of water is not always the same, but changes, not only in the course of one 
febrile disease, but also in different forms of fever. Correspondingly, the role played 
by the nervous system in the occurrence of the feverish increase of temperature is not 
the same in every case. According to Senator, there is, in fevers, no harmony between 
the regulation of heat and metabolism ; and we must therefore assume that heat is de- 
veloped through other processes than those leading to the production of urea and car- 
bonic acid. According to Herz, heat is set free by the changes in the arrangement of 
the nwlecules of the cell-protoplasm, which occur in many of the cells in fever patients, 
and which lead to the destruction of protoplasm. Further, heat may be liberated by 
l)rocesses of swelling and coagulation of the protoplasm, while at the same time the 
diminished activity of the regenerative processes in fever occasions a loss in the stor- 
ing-up of latent heat. On the other hand, Erehl and Marthes are of the opinion that 
oxidation forms the sole source of heat. 
7 



98 EFFECTS OF ORGANIC DISEASES UPON THE ORGANISM AS A WHOLE. 



Literature. 

(Fever.) 

Aronsolin u. Sachs: Beziehungen d. Gehirns zur Korperwarme u. zum Fieber. 

Pfliiger's Arch., 37 Bd., 1885. 
Bouchard: Lecons sur les auto-intoxications dans les maladies, Paris, 1889. 
Cohnheim: Vorlesungen iiber allgemeine Pathologic, ii., Berlin, 1882. 
Finkler: Pfliiger's Arch., xxvii. ; Ueber das Fieber, Bonn, 1882. 
Franke: Die menschliche Zelle, Leipzig, 1893. 

A. Frankel: Einfluss verminderter Sauerstf)f[:zufuhr auf den Eiweisszerfall. Virch. 
Arch., 67 Bd. 

Gangolphe et Courmont: La fievre consec. a Pobliteration vasculaire. Arch, de 
nied. exp,, iii., 1891. 

Gerhardt: Oertliche Fieberursachen. Mittheil. a. d. med. Klinik zu Wlirzburg, Wies- 
baden, 1885. 

Girard: L'influence du cerveau sur la chaleur animale. Arch. d. phys., viii., 1886. 
Glax: Ueber die Wasserretentiou im Fieber, Jena, 1894. 

Guyon: L'hyperthermie centrale, consec. aux les. du cerveau. Arch, de med. exp., 
1894. 

Hammerclilag : Bezieh. des Fibrinfermentes zum Fieber. Arch. f. exp. Path., 27 
Bd.,1890. 

Henrijean: Rech. sur la pathogenic de la ti^vre. Rev. de med., ix., 1889. 
Herz: Uutersuchungen liber Warme und Fieber, Wien, 1893. 

Hildebrandt : Z. Kenntniss d. phys. Wirkung d. hydrolytischen Fermente. Inaug.- 

Diss., Breslau, 1890. 
Jiirgensen: Die Korperwarme des gesunden Menschen, Leipzig, 1878. 
Kreh.1 : Pathologische Physiologic, Leipzig, 1898. 

Krehl u. Matthes: Entstehung der Temperatursteigerung des fiebernden Organismus. 

Arch. f. exp. Path., 38 Bd., 1897 (Lit.); Eiweisszerfall, ib., 40 Bd., 1898. 
Leyden: Respiration im Fieber. Deut. Arch. f. klin. Med., v., vii., 1870. 
Leyden u. Frankel; Respiratorischer Gasaustausch im Fieber. Virch. Arch., 76 Bd., 

1879. 

Liebermeister : Pathol, u. Ther. d. Fiebers, Leipzig, 1875; Speciellc Pathol., Leip- 
zig, 1887. 

Lowit: Die Lehre vom Fieber, Jena, 1897. 

Loewy: StoSwechseluntersuchungen im Fieber. Virch. Arch., 126 Bd., 1891. 

May: Der Stoffwechsel im Fieber. Zeitschr. f. Biol., 30 Bd., 1893. 

Mosso: Influence du systeme nerveux sur la temperature animale. Arch. ital. de 

bioL, vii., 1886; Virch. Arch., 106 Bd. ; La doctrine de la fievre et les centres 

thermiques cerebraux. Arch. ital. de biol., xiii., 1890. 
Murri: Sulla teoria della febbre, Fermo, 1874. 

Naunyn: Experimentelles zur Lehre vom Fieber. Arch. f. exp. Path., xviii.,, 
1884 (Lit.). 

V. Noorden: Pathologic des Stoffwechsels, Berlin, 1893. 
Rabe: Die modernen Fiebertheorieen, Berlin, 1894. 
Rosenthal : Warmeproduction im Fieber. Biol. Cbl., xi.. 1891. 
Roussy : Rech. exp. sur la pathogenic de la fievre. Arch, de phys., ii., 1890. 
Sarbo: Ueber hysterisches Fieber. Arch. f. Psych., 23 Bd., 1891. 
Schultze: Warmehaushalt nach dem Warmestich. Arch. f. exp. Path., 43 Bd., 1899. 
Senator: Unters. taber den fieberh. Process, Berlin, 1873; Arch. f. Anat, u. Phys., 
1872. 

Stern: Warmeregulation im Fieber. Zeitschr. f. klin. Med., 20 Bd., 1892. 
Ughetti: Das Fieber, Jena, 1895 (Lit.). 
Unverricht: Ueber das Fieber, Leipzig, 1898. 

Volkmann u. Genzmer: Septisches u. asept. Wundfieber. Samml. klin. Vortr., No„ 
121, 1877. 

Welch : On the General Pathology of Fever, Philadelphia, 1888. 
Wunderlich: Das Verhalten der Eigenwarme in Krankheiten, Leipzig, 1870. 
Zunz : Ueber den Stoff wechsel fiebernder Thiere. Arch, f . Psych. . 1882. 



CHAPTER III. 



The Protective and Healing Forces of the Human 
Body. The Acquiring of Immunity. 

I. The Natural Protective Contrivances, Protective Forces, and 
Healing Powers of the Human Organism, and their Action. 

§ 29. The human organism is not entirely defenceless against the 
many harmful influences to which men during the course of their lives 
are exposed. It possesses various protective contrivances and pro= 
tective forces, by which it is able in many cases to ward off the injuri- 
ous agent, or at least rapidly to counteract its harmful influence, so that 
a disease may be either wholly prevented or confined to a slight local 
lesion of much less severity than the disease usually produced by the 
particular injurious agent. As the mode of action of different injurious 
influences varies greatly, so does the manner of defence likewise vary 
greatly. The protective forces may act at very different times — that is, 
sometimes even before the tissues have been damaged, at other times 
after the injurious action has reached a certain stage, and threatens, 
either through direct extension or through metastasis, or through poison- 
ing of the body-fluids, or through disturbance of function, to spread 
further through the body. 

When the environment of the body becomes relatively cold or rela- 
tively warm, those regulating functions are brought into play through 
which the organism can increase or diminish heat-production a^id heat-dis- 
persion, and in this manner protect itself within certain limits against 
the influence of the external temperature. If these regulating functions 
are imperfectly performed, as in consequence of alcoholic intoxication, 
the individual may more easily die from the effects of cold than when 
under normal conditions. 

We cannot speak of special protecting contrivances against gross 
mechanical iiijlueiices ; yet it is to be noted that the tissues by virtue of 
their physical properties are fitted to offer resistaiice to numerous forms 
of traumatism without receiving injury. If small, firm bodies, such as 
dust-particles, reach the mucous membrane of the respiratory or intes- 
tinal tracts, the epithelium forms a protective barrier against their en- 
trance into the tissue -spaces. Further, if ciliated epithelium is present, 
the dust -particles may be carried away by the moveinents of the cilia, or 
they may become surrounded by the mucus produced by the epithelium 
and mucous glands, and in this way are transported out of the body. 

^^'ot infrequently there appear cells on the surface of the mucous 
membrane which encompass the dust-particles, and, taking these up into 
their substance, are carried away with the secretion of the mucous mem- 
brane. This phenomenon, known as phagocytosis, is observed on the 
mucous membranes of the pharynx and respiratory tract and in the 
alveoli of the lungs. The active agents participating in it are not only 
L.cfC. 99 



100 



THE PROTECTIVE POWERS OF THE BODY. 



the wandering-cells whieli pass from the tissues to the surface, and are 
derived chiefly from the blood-vessels and also from the nodes of 
lymphadenoid tissue in the mucous membrane, but epithelial cells as 
well. The peculiar phenomenon of phagocytosis depends upon the fact 
that the cells can, by movements of their protoplasm, take up little par- 
ticles, which, like insoluble dust, exert no harmful influence upon the 
cell-protoplasm. If these cells laden with dust pass outside of the body, 
the taking-up of the dust by the cells appears to be a useful activity 
which aids in the cleansing of the organs from dust. If the dust-laden 
cells, on the other hand, as happens particularly in the lungs, pass into 
the lymph -channels and are deposited along their walls or are carried to 
the lymph-glands — that is, if a metastasis of the dust-containing cells 
into the internal organs takes place — the taking-up of dust by these cells 
appears in a less favorable light ; and Ave can regard this act as a useful 
phenomenon only through the consideration that the infiltration of the 
pulmonary connective tissue and lymph-glands with dust is less harmful 
than the deposit of dust on the inner surface of the alveoli. 

When dust-particles, free or enclosed in cells, reach the lymph-glmids, 
they are arrested and deposited in the cells of these glands, so that the 
lymph -glands may be regarded as trustworthy filters, which guard the 
blood and the internal organs from the entrance of dust. 

Against the action of poisons the human body is able to protect itself 
in various ways. In the case of corrosive poisons the liorny layer of the 
epidermis and the mucus of the mucous membranes offer a certain pro- 
tection ; and under certain conditions a marked increase in the produc- 
tion of mucus — in the stomach, for example — may greatly diminish 
the harmful effects of a corrosive fluid: Through a transudation of fluid 
from the blood-vessels on to the surface of the mucous membrane a 
caustic fluid may be so diluted as to modify its action. On the other 
hand, the injurious substance may be thus spread over a greater surface, 
and thereby cause a more widespread damage to the tissue. 

On many poisons, abrin, ricin, the toxins of cholera, tetanus, and 
diphtheria, and snake- venom, the digestive juices have such an influence 
that doses invariably fatal when injected under the skin may be borne 
with impunity when taken by the mouth. According to Eansom, 
guinea-pigs are able to withstand, when administered by the mouth, an 
amount of tetanotoxin equivalent to three hundred thousand times the 
minimal fatal dose. According to N'encki and others, this neutralization 
of the poison is produced by the digestive enzymes, at one time chiefly through 
the pepsin, at another time through the trypsin and the mixture of the 
pancreatic juice with the bile. It is probable (^sTeucki) that the digest- 
ive enzymes cause a slight change in the molecules of the toxin, similar 
to the change of albumin into albumose ; and the products arising from 
the toxins may accordingly be termed toxoses or toxoids. 

In the case of those poisons which after their entrance into the body- 
juices act injuriously upon the blood or the nervous system, a favorable 
counter action on the part of the organism may be given partly by a 
rapid excretion of the poison through the kidneys, liver, and intestine, 
and partly through a chemical change of the poison. This method of pro- 
tection is effective only when it is accomplished before any injury has 
been produced by the poison. 

Of natural immunity against poisons or natural resistance to poisons we 
know but little at present, yet there is no doubt that many poisons are 
poisonous only for certain organisms, and it is probable that man is re- 



THE PROTECTIVE FORCES AGAINST INFECTION. 



101 



sistant to many poisons which are injurious to certain animals. The 
same thing holds true especially of the toxic proteids and the organic 
bases, as they are formed by bacteria or by higher animals (snakes) and 
plants. If we consider that many animals are only slightly or not at all 
susceptible to poisons which have marked action upon the human body 
— for example, the hedgehog is immune or resistant to cantharidin and 
the bite of poisonous snakes respectively; birds are immune against 
atropine and opium ; goats against lead and nicotine ; while dogs, rats, 
or other animals used for experiment show a disproportionately greater 
resistance to bacterial poisons or plant-alkaloids than does man — so it is 
very probable that the reverse is also true. The natural immunity of 
man against many of the infectious diseases of animals must depend 
upon a resistance to the toxalbumins and toxins produced by the par- 
ticular bacteria. According to Ehrlich, this resistance to poisons may 
be explained by the theory that the particular toxin possesses no chemi- 
cal relationship to any one of the bodily elements. 

Literature. 

(^The Action of Digestive Juices upon Toxins.^ 

Charrin: Action des sues digestifs sur k'S poisons mierob. Areli. d. phys., x., 1898. 
Fraser: Remarks on the Anti venomous Properties of the Bile. Brit. Med. Journ., 
1897. 

Nencki, Sieher u. Schoumow: Entgiftung d. Toxine durch Verdauungssafte. Ctbl. 
f. Bakt., xxiii., 1898. 

Ransom: Das Scliicksal des Tetaniisgiftes nach seiner intestinalen Einverleibimg. 
Deut. med. Woch., 1898. 

§ 30. Against the infections and intoxications caused by parasites 

the human organism possesses various protective contrivances and 
powers of defence ; and these play a very important role in the diseases 
caused by bacteria. In the first place, man possesses a natural im= 
munity against many of the micro-organisms pathogenic for animals 
(for example, swine-plague, swine-erysipelas, symptomatic anthrax), so 
that the given micro-organisms are not able to reproduce within the 
body, either because they do not find in human tissues the necessary 
conditions of life, or because the presence of certain chemically active 
substances hinders their increase or kills them directly. For the protec- 
tion of the body against the pathogenic micro-organisms there are avail- 
able certain forces, which, according to their activity, may be divided 
into four groups : the first hindering the entrance of bacteria into the 
tissues ; the second hindering the unlimited local spread of those bacteria 
which have gained entrance and have begun to multiply ; the third pre- 
venting the entrance of bacteria into the blood and their metastasis ; the 
fourth hindering intoxication, or at least weakening it, and reducing it 
to a low degree. 

For the prevention of the entrance of pathogenic bacteria into the 

tissues the same properties of tissues are effective as those hindering the 
entrance of dust ; and in such capacity the lyrotective epithelium and the 
mucus play a very important role. In the respiratory tract the move- 
ments of the ciliated epithelium also furnish protection, and in the stomach 
the poisonous action of the gastric juice upon many pathogenic bacteria is 
an efficient means of defence. There can be no doubt that many patho- 
genic bacteria are not able to penetrate into the tissues, not only through 



102 



THE PROTECTIVE FORCES AGAINST INFECTION. 



the uninjured external skin, but also through an unwounded mucous 
membrane, without some assistance favoring colonization and reproduc- 
tion, and that the stomach secretion not infrequently hinders the activity 
of the bacteria (pneumococcus, cholera spirillum), or even kills them. 

It appears also that the mucus secreted by the mucous membranes not 
only can envelop the bacteria, hinder their entrance into the tissue, and 
favor their removal, but that — what is of much greater importance — the 
mucus acts upon the bacteria, causing them to degenerate, either in that 
it contains substances which are injurious to the bacteria or in that it 
offers an unfavorable medium for the growth of the bacteria. In this 
way, according to Sanarelli and Dittrich, pus-cocci, cholera-spirilla, and 
pneumococci gradually lose their virulence and die in the mucus of the 
mouth-cavity, while diphtheria-bacilli apparently are not injured by 
mucus. In the secretion of the vagina and uterus, various kinds of bac- 
teria likewise soon die. 

^^^ot every pathogenic organism, therefore, which gains a foothold 
upon the skin or upon any of tlie accessible mucous membranes or gains 
entrance to the lungs produces an infection. It has been shown through 
repeated investigations that in normal individuals there not infrequently 
occur in the upper respiratory passages and mouth-cavity not only harm- 
less bacteria — i.e., those which cannot reproduce in human tissues — but 
also those which can undoubtedly produce disease, as, for example, cocci 
which cause suppuration or those which are able to cause croupous in- 
flammation of the lung. It is, therefore, to be assumed that bacteria 
which are found upon the mucous membranes and have perhaps multi- 
plied there often die and are carried away without having produced in- 
fection. This occurs especially in the case of the cocci above mentioned, 
and tubercle -bacilli, as well as in the case of cholera-spirilla which suffer 
when brought into contact with the acid secretions of the stomach. Fin- 
ally, it may also be assumed that of the pathogenic bacteria entering the 
alveoli of the Inng in the inspired air, many do not reproduce but die. 

In the case of a wound, uninjured icound- granulations offer a relatively 
secure protection against infections ; in the first place, mechanically^, by 
means of the thick layer of cells (Noetzel) ; and further, from the fact 
that the tissue-juices which escape from the granulations and infiltrate 
the same may weaken the virulence of various bacteria (Afanassieff). 

When bacteria have succeeded in gaining entrance locally and 
have begun to multiply — no matter whether they have iDassed through 
the epithelium without the aid of any other influence (typhoid-bacilli, 
cholera-spirilla), or whether they have passed into the connective tissues 
through the medinm of small wounds (tetanus- bacilli, pus-cocci, cocci of 
erysipelas, tubercle-bacilli) — if they produce further effects either 
through local destruction of tissue or through the poisoning of the fluids 
of the body, there may be brought into action on the part of the body 
certain counter=infIuences tuliicli either hinder the further development of 
the bacteria or iveaJcen or even completely destroy the poisons produced by 
them. The first-named restraining influence must naturally depend upon 
local conditions, either upon vital tissue-processes or upon the efl'ects of 
chemical substances. 

As previously mentioned, the development of bacterial colonies gives 
rise to, local tissue -degenerations, inflammation, and tissue -proliferations 
— all of which are processes in which the amount and composition of the 
fluids found in the affected region, as well as the cells themselves, are 
changed. Since in some of these cases a destruction of the bacteria has 



PHAGOCYTOSIS : PROTECTIVE POWERS OF THE BLOOD AND LYMPH. 103 

been observed, and the infection not infrequently comes to an end 
through the complete disappearance of the bacteria, the death of the 
latter must be regarded as dependent upon local conditions. 

Many writers ascribe the prevention of the further spread of the 
infection and the destruction of the bacteria, in local foci of growth, to 
the activity of cells which collect at the seat of infection and take up the 
bacteria into their protoplasm — that is, to phagocytosis is ascribed the 
most important role in the protection of the body against bacterial in- 
vasion. According to Metschnikoff and others, the amoeboid cells of the 
body carry on a fight against the foreign invaders and endeavor to over- 
come them and destroy them. Such a characterization of the phenomena 
of phagocytosis is not supported by the actual facts, and can be regarded 
only as a poetical manner of expression by which consciousness and will- 
power are attributed to the amoeboid cells of the body (the leucocytes 
and the proliferating tissue-cells) — which attributes it is evident do not 
exist. Scientifically considered, the gathering of the cells at the infected 
focus and the resulting phagocytosis represent simply an expression of 
certain processes which are natural to the amoeboid cells, and which are 
dependent upon the fact that the cells under the influence of mechanical, 
chemical, and thermal influences perform certain definite movements. 
We know through numerous investigations that the motile cells of the 
body are in part attracted, in part repelled or paralyzed by means of 
chemical substances in certain concentrations of solution (see the Chapter 
on Inflammation) ; and, further, that contact with hard bodies can stim- 
ulate them to the sending-out of protoplasmic processes. 

Such phenomena are designated as negative and positive chemo= 
tropismus or chemotaxis and as tactile irritability. We must assume 
that the bacteria multiplying within the tissues act upon the amoeboid 
cells through the chemical substances which they produce, sometimes re- 
pelling or paralyzing, sometimes attracting, in the latter case affording 
conditions favorable for phagocytosis. This assumption is in harmony 
with the actual behavior of the cells in different local infections, in that 
the bacteria in one case are taken up by the cells, in another they are 
left undisturbed. 

If phagocT/tosis of the cells, in infections, be regarded as one of the 
vital phenomena of cells, it may be interpreted as ^ process designed for 
the taking-up of nourishment ; and this interpretation would suffer only 
one exception, whenever microparasites, themselves capable of motion, 
penetrate by reason of their own activity into the cells. 

The result of the taking-up of bacteria into cells depends in a particular 
case x^artly upon the properties of the devouring cells, partly upon the 
properties of the microparasites, and can result as well in the death and 
dissolution of the parasite, as in the death of the cells ; or in a symbiosis 
of the cells with the parasites, the latter living within the cells un- 
changed and giving rise to no disturbance. In the first-named case the 
phagocytosis may be regarded as a curative process which hinders the 
multiplication and spread of the bacteria. In the second and third 
cases, on the contrary, the phenomenon is useless for the prevention of 
the spread of the parasites; indeed, there are cases (lei^rosy and to some 
extent also tuberculosis) in which the parasites find favorable conditions 
for development inside of the cells, increase within them, and finally 
cause their destruction. If the cells containing bacteria* remain pre- 
served for a length of time, they may wander with the enclosed bacteria 
to other parts of the body, in this way effecting a metastasis. 



104 



THE PROTECTIVE FORCES AGAINST INFECTION. 



Phagocytosis is therefore 07ily of slight significance as a protective force in 
a certain number of cases ; yet it cannot be doubted tbat the phagocytes in 
certain infections take up, not only dead or dying, but also living bac- 
teria not yet injured by other agents, and can cause their death. The 
collection of great numbers of cells in the infected tissue may, through 
the close packing of the lymphatics, offer a certain mechanical hindrance to 
the spread of bacteria, yet the protection so afforded is frequently in- 
sufficient. 

If bacteria, either free or enclosed in cells, pass from the lymph- ves- 
sels into the lymph=glands, the latter act as filters, as in the case of 
dust, and retain the bacteria; but the protection which they offer is 
sufficient only when the bacteria so collected in the lymph -glands are 
hindered in their reproduction and are killed by the influence of their 
surroundings. The destruction may be accomplished under the influence 
of phagocytosis, but in many cases phagocytosis is possible only tvhen the bac- 
teria a/re weakened or have already been killed. Further, the taking-up of 
living bacteria by the cells is not always followed by destruction of the 
bacteria, but there very frequently takes place an intracellular multipli- 
cation of the bacteria. 

More important than phagocytosis for the prevention of the spread 
of bacteria and other microparasites is the influence exerted by certain 
chemical substances in solution in the tissues. Since the saprophy- 
tic, non-i3athogenic bacteria, when injected into living tissue, are killed 
within a very short time, we must assume that in the tissues there are 
present chemically active substances which are poisonous for many bacteria and 
can cause their rapid destruction. Further, since many pathogenic bac- 
teria ordinarily increase only locally (tetanus-bacilli, dii^htheria-bacilli, 
cholera-spirilla) and after a certain time perish within the infected area, 
without spreading further through the body, it is very probable that the 
tissues of the body also contain substances which are poisonous for 
many pathogenic bacteria and prevent their spread. The phenomena 
observed in local infections si^eak also for the fact that such substances 
at times are formed in increased amounts or are aided in their action by 
newly-formed poisonous substances. It is, furthermore, probable that 
the crowding of cells which takes place in the infected tissue or in its 
neighborhood leads also to an increase in the production of these poison- 
ous substances, and may thereby hinder the spread of the bacteria ; nev- 
ertheless, attention should be drawn to the fact that in many infections 
the spread of bacteria through the tissues comes to a standstill in places 
where there has been no crowding together of cells. It is also a fact 
that in many infections the spread of bacteria through the body by 
metastasis is either wholly wanting (tetanus, diphtheria) or at least is 
insignificant in comparison with the local infection, and is usually fol- 
lowed by relatively insignificant local changes. The explanation of this 
fact is to be sought, not so much in the assumption that local tissue- 
changes, through the formation of special chemical substances or through 
the aid of mechanical substances or through the aid of mechanical hin- 
drances — such as that afforded by a wall of cells — hinder the entrance of 
bacteria into the lymph and blood, but much more in the fact that there 
are present in the lymph and blood itself certain forces ivhich are able to in- 
jure and weaken the bacteria taken up into these fluids or to destroy 
them. 

The hostile action of the blood on bacteria has been ascribed to the 
phagocytic action of the leucocytes ; and this theory is supported by the 



PHAGOCYTOSIS: ANTIBACTERIAL PROPERTIES OF THE BLOOD. 105 

fact that such a phagocytosis can be demonstrated very frequently in 
acquired infectious or after the artificial introduction of bacteria into the 
blood ; and, further, by the fact that the bacteria within the blood, en- 
closed in cells, may often be carried out of the blood-vessels and deposited 
in different organs— for example, the spleen, liver, bone-marrow, and 
the kidneys — and there destroyed or excreted from the body. These 
observations do not warrant the conclusion that phagocytosis forms a 
protection against the spread of bacteria in the lymph and blood ; in- 
deed, in those very cases in which a transportation of bacteria through 
the blood does not take place, phagocytosis is also absent ; while on the 
contrary, the entrance of bacteria into the blood, and the multiplication 
of the same inside of the blood-vessels, is \^ery often accompanied or fol- 
lowed by phagocytosis. Here, again, phagocytosis is of the nature of a 
secondary phenomenon which occurs when there are present in the blood 
bacteria or protozoa, which like bland dust-particles are not able to pre- 
vent their being taken up into the bodies of the leucocytes — that is, they 
exert a positive attraction on the phagocytes. 

When bacteria are taken up by cells, they either die or continue to 
multiply inside of the cells, according to their properties and their con- 
dition at the time of the phagocytosis. 

The forces which are able to hinder the development of bacteria in 
the Uood are believed by the majority of writers to depend upon the 
presence of antibacterial chemical substances, which belong to the 
albuminoid bodies, and are designated as the protective albuminoid 
bodies or alexins (Buchner) or mycosozins (Hankin). 

Emmerich and Buchner assume that the alexins of the blood are 
albuminoid bodies, having an action similar to that of enzymes, and 
therefore class them with the enzymes. This view finds acceptance 
with other authors. On the other hand, Baumgarten and Walz, as well 
as A. Fischer, oppose the view that there are chemically active pro- 
tective substances in the blood ; and hold that the natural immunity of 
the tissues and blood against certain bacteria is dependent upon the fact 
that the bacteria do not find the necessary chemical conditions for their 
development and reproduction. 

So far as conclusions can be drawn from the behavior of the human 
and animal organisms in infectious diseases, we may assume that in tJie 
blood of man there are always present 'protective chemical substances, that is, 
alexins, particularly so against bacteria which never or only exception- 
ally enter the blood; and that others, on the contrary, are produced only 
during the course of an infection, so that not until a certain stage of the 
infection does an inhibition of the development of the bacteria, through 
the formation of antibacterial substances, occur. In favor of such 
hypothesis speaks the fact that many bacteria (typhoid-bacilli, cholera- 
spirilla, pus-cocci) possess at first their full virulence when distributed 
through the body by the blood, but later suffer a loss of virulence and 
finally die. 

The protection which the alexins of the blood afford the organism is 
restricted to certain diseases ; that is, to those infections in wliich the 
multiplication of the bacteria is always confined to a limited area, or in 
which at least the transported bacteria suffer a marked decrease of viru- 
lence. Against many infections the peculiar degenerative action of the 
blood upon bacteria is either wholly wanting or, in case it is present, i& 
easily overcome, especially so in those infections in which the bacteria 
increase in the blood itself (anthrax), as well as in those in which the 



106 



THE PROTECTIVE FORCES AGAINST INFECTION. 



bacteria do not increase in the blood, bnt suffer no decrease of virulence 
after metastasis (tuberculosis, leprosy, infections with pus-cocci). 

The means of protection which the organism possesses against the 
poisons produced in the tissues by bacteria are to be found, first, in 
the possibility of a rai)id excretion of the poisons by the kidneys, or, 
under certain circumstances, also by the stomach, intestine, and skin; 
and this action may in certain cases suffice to prevent a fatal poisoning. 
Further, in certain infections there is evidently an antagonistic action on 
the part of the organism, in the sense that certain poisons are either 
destroyed or neutralized through the action of counter poisons or 
antitoxins ; or that the toxins and antitoxins combine to produce 
non-poisonous substances, or that the metabolic products of the tissues 
protect the latter from the action of the toxins. 

The antihacteri(d properties of the hloocl and lymph against certain bacteria have been 
demonstrated conclusively by the experimental investigations of various writers. 
These experiments have shown that the bactericidal action of the blood of a given ani- 
mal is exerted only upon certain forms of bacteria and never upon all ; and that this 
action is subject to individual variations. 

According to the investigations of Fodor, Petruscliky , Nuttal, Ogata, Bucliner, Beh- 
ring, JVissen, Pansini, and others, the blood and the serum from dogs, rabbits, and 
white rats are capable of rendering the anthrax-bacillus harmless, and even of killing it; 
but this action is a limited one, so that after the introduction of a large number of the 
bacilli into the blood taken from the vessels, the bacilli after a time begin to multiply. 
Detibrinated blood of dogs and rabbits can destroy the cholera-spirillum and typhoid- 
fever bacillus; but, on the other hand, has no effect upon the different pus-cocci, and 
against proteus; the same is true also Avith regard to the blood-serum. Human blood 
or blood-serum can kill tj^Dhoid-bacilli, diphtheria-bacilli, and the bacilli of glanders. 
If the bactericidal properties be exhausted, these bacteria may grow luxuriantly in the 
blood or serum. Heating of the blood-serum to 55° C. deprives it of its bactericidal 
properties; the enzyme is destroyed {Bucliner). 

According to Afoxter, there are two substances concerned in the bactericidal action 
of the animal fluids; one of which disappears at a temperature of 60° C, while the 
other remains preserved. 

Baumgartcii and ^Valz regard the fact that different bacteria which have been 
passed into the blood or blood-serum do not develop at all, or show but partial or de- 
layed growth and a great diminution in numbers when cultivated upon plates, as in no 
manner speaking for the presence of bactericidal substances in the blood. According 
to their view, the second transplantation into another culture-medium causes a disturb- 
ance of the processes of assimilation and osmosis. There arise in consequence plasmo- 
lytic changes in the bacteria present in the serum; during the pouring of the plates the 
already injured cells die from disturbances of assimilation. This view is also held, 
supported by experimental investigations, by A. Fischer. On the other hand, it is to 
be noted that A. and H. Kossel have demonstrated that certain products of animal 
cells jnucleinic acid, protamine) possess bactericidal properties. 

Rankin, Kanthack, Denys, Hahn, Lowit, and others assume, on the ground of ex- 
perimental investigations, that the alexins are produced hy the leucocytes. Kossel holds it 
as possible that the nucleinic acid present in the leucocytes in relative! rich amounts 
plays a role in the destruction of the bacteria. JSoesske believes that the eosinophile 
cells of the bone-marrow in particular produce bactericidal substances. It is not possi- 
ble at the present time to draw a detinite conclusion as to the part played by the color- 
less cells of the blood in the defence against infections. 

According to Bitter, the bactericidal substance found in organs — that derived from 
the lymph-glands, spleen, and thymus— is to a certain extent different from that of the 
blood and tlie blood-serum, and therefore does not originate whollj^ in the blood. It is 
certain that the bactericidal action of the blood is not the only protective influence 
which can oppose the spread of an infection, or wholly prevent it, and confer im- 
munit5\ 

According to observations of Czaplewski, anthrax -bacilli in an infected organism, 
which have been taken up into leucocytes, degenerate as a rule more slowly than those 
lying free in the blood and tissue-juices. It appears, therefore, as if under certain con- 
ditions the cells afford to the bacteria which they enclose a certain degree of protection 
from the bactericidal substances of the tissue-fluids. 

The antitoxins which render the bacterial poisons harmless are usually formed first 



THE PROTECTIVE FORCES AGAINST INFECTION. 107 



during the course of the infection; but, according to the investigations of Wasser- 
naann, Abel, Fiscld, von Wunschheim, and others, the serum of healthy men also con- 
tains such substances. Serum which contains the antitoxin against a certain toxin — 
as, for example, that against the diphtheria-toxin — can be a good culture-medium for 
the given bacteria ; the antitoxin does not destroy the bacteria. 



Literature. 

( The Protective Foiver of the Body against Infection. ) 

Afanassieff: Bedeutung d. Granulationsgewebes bei Infectionen. Beitr. v. Ziegler, 
xxii., 1897. 

Arloing": Un mot sur I'immunite naturelle. Arch, de med. exp., 1890; Les virus, 
Paris, 1891. 

Arnold: Der Kampf d. menschl. Organismus mit d. Bakterien. Akad. Rede, Heidel- 
berg, 1888. 

Baumg-arten : Der gegenwartige Stand der Bakteriologie. Berl. klin. Woch., 1900; 
Die natiirl. Schutzmittel geg. Infection, ib., 1900; Verliandl. d. D. path. Ges., ii., 
Berlin, 1900. 

Behring": Infection und Desinfection, Leipzig, 1894; Infectionsschutz u. Immunitat. 

Eulenb. Jahrb., ix., 1900. 
Behring u. Nissen: Bakterienfeindl. Eigenschaften verschied. Blutserumarten. Zeit. 

f. Hyg., viii., 1890. 

3esredkaj Pouvoir bactericide des leucocytes. Ann. de I'lnst. Pasteur, xii., 1898. 

Bitter: Ueb. d. bakterienfeindlichen Stofi'e thierischer Organe. Zeit. f. Hyg., xii., 1891, 

Bordet; Rech. sur la phagocytose. Ann. de I'lnst. Pasteur, 1896. 

Brock: Resorptionsvermogen der Haut. Arch. f. Derm., 35 Bd., 1898 (Lit.). 

Buchner: Ueber die bakterientodtende Wirkung des freien Blutserums. Centbl. f. 
Bakt., v., vi., 1889; Ueber die bakterientodtende Wirkungen d. Blutes u. Blut- 
serums. Arch. f. Hyg., x., 1890, ref. Cbl. f. Bakt., ix.; Hulfskrafte d. Organ- 
ismus gegen Krankheitserreger. ]\Iunch. med. Woch., 1894; Bakteriengifte und 
Gegengifte, ib., 1893; Natiirl. Schutzeinrichtungen, ib., 1899. 

Charrin: Les defenses naturelles de I'organisme, Paris, 1898. 

Czaplewsi: Unters. lib. d. Immunitat der Tauben gegen Milzbrand. Zeit. f. Hyg., 

xii. , 1892. 

Emmerich, u. di Mattei: Vernichtung d. Milzbrandbacillen im Organismus. Fortschr. 
d. Med., v., 1887. 

Emmerich u.Tsuboi: Die Schutz- u. Heilkrafte des Blutes. Verh. d. XI. Kongr. f, 
inn. Med., Wiesbaden, 1892; Mikrobicide Wirkung des Blutserums. Cbl. f. Bakt., 

xiii. , 1893. 

Fischer, A. : Die Emptindliclikeit d. Bakterienzelle u. d. baktericide Serum. Zeit. 
f. Hyg., 35 Bd., 1900. 

Fischl u. V. Wunschheim: Schutzkriifte im Blute d. Neugeborenen. Zeit. f. 
Heilk., 1895 (Lit.). 

-V. Fodor: Die Fahigkeit d. Blutes, Bakterien zu vernichten. Cbl. f. Bakt., vii., 1890. 
Friedenthal: Function der weissen Blutkorperchen. Biol. Cbl., xvii., 1897 (Lit.). 
Gabritschewsky: Pathologic der Spirochateninfection. Cbl. f. Bakt., xxiii., 1898. 
Bankin: Ueber den schiitzenden Eiweisskorper der Ratte. Cbl. f. Bakt., ix., x., 

1891 ; Ueber den Urspruug und das Yorkommen von Alexinen im Organismus, ib., 

xii., 1892. 

Hugenschmidt : Defense de la cavite buccale. Ann. de I'lnst. Pasteur, 1896. 
Jacob: Schutzkraft d. Leukocyten. Zeit. f. klin. Med., 32 Bd., 1897. 
Jetter: Baktericide Eigenschaften des Blutserums. Arb. a. d. path. Inst, zu Tiibin- 
geu, i., 1893. 

Kendratiefif: Selbstschutz des thier. Organismus. Arch. f. exp. Path., 37 Bd., 1896. 
Kossel: Lymphzellen. Deut. med. Woch., 1894; Baktericide Zellbestandtheile. Zeit. 

f. Hyg., 27 Bd., 1898. 
Krosing: Bakterienfeindliches Verhalten d. Scheidensecrete. Deut. med. Woch.. 1894. 
Kruse: Bemerkungen iiber Infection, Immunitat, und Heilung. Beitr. v. Ziegler, 

xii., 1893. 

Kiister: Fragen der pathol. Pflanzenanatomie. Biol. Cbl., xx., 1900. 

Xondon: L'action bactericide du sue gastrique. A. des sc. biol., v., 1897; Proprietes 

bactericides du sang, ib., v., 1897. 
Xiowit: Bezieh. d. Leukocyten zur baktericidcn Wirkung. Beitr. v. Ziegler, xxii., 

1897. 

Xtubarsch: Die bakterienvernichtenden Eigenschaften des Blutes. Cbl. f. Bakt., vi.. 



108 



HEALING POWERS OF THE BODY. 



1889 ; Unters. lib. die Ursachen der angeborenen und erworbenen Immunitat, Ber- 
lin, 1891. 

Manfredi: Bedeutimg d. Lymphgangliensystems. Vircli. Arch., 155 Bd., 1899. 

Marchand: La pliagocytose des streptocoques. Arcli. de med. exp., x., 1898. 

Marmorek: Tlieorie der septischen Krankheiten, Stuttgart, 1894. 

Metschnikoff: Patliologie comparee de rintiammation, Paris, 1892. 

Mills: Action de la salive et du sue gastr. sur les bacteries, Bruxelles, 1896. 

Mosse: Kommen der Zelle antibakt. Eigensch. zu? Zeit. f. klin. Med., 36 Bd., 1898. 

Moxter: Wirkungsweise der bakterienautlos. Substanzen. Cbl. f. Bakt., xxvi., 1899; 

Beziehung d. Leukocyteu zu den bakterienautloseuden Stotfen. Deut. med. Woch., 

1899. 

Neisser: Durchgangigkeit der Darmwand fiir Bakterien. Zeit. f. Hyg., xxii., 1896. 
Nissen: Bakterienfeindl. Eigensch. d. Blutes. Zeitsclir. f. Hyg., vi., 1889. 
Noesske: Eosinophile Zellen bei Infectiouskrankheiten. Zeit. f. Chir., 55 Bd., 1900. 
Ndtzel: Infect, granul. Wuuden. Forschr. d. Med., xvi., 1898. 

Nuttal: Bacillenfeindl. Einfiiisse des thier. Korpers. Zeit. f. Hyg., iv., 1888; Bak- 
terien vernichtende Eigenschaften des Blutes. Cbl. f. Bakt., iv., 1889. 

Og-ata: Ueber die bakterienfeindliche Substanz des Blutes. Cbl. f. Bakt., ix., 1891. 

Pekelharing" : Zerstorung des Milzbrandvirus im Unterhautbindegewebe. Beitr. v. 
Ziegler, viii., 1890. 

Petruschky: Der Verlauf der Phagocytencontroverse. FortSchr. d. Med., viii., 1890;. 
Einwirkungdeslebenden Froschkorpers auf den Milzbrandbacillus. Zeit. f. Hyg., 
vii., 1889. 

Podwyssozki : Die Reservekrafte des Organisraus, Jena, 1894. 

Sanarelli: Die Ursachen der natlirl. Immunitat gegen Milzbraud. Zeit. f. Bakt,, ix., 
1891; Defense de I'organisme centre les microbes. Ann. de I'lnst. Pasteur, vii., 
1893. 

Stern: Ueber die VVirkung des menschlichen Blutes und anderer Korpertlilssigkeiten 
auf pathogene Mikroorganismen. Zeit. f. klin. Med., 18 Bd., 1890; Neuere 
Ergebnisse auf dem Gebiete der Immunitatslehre. Cbl. f. allg. Path., v., 1894 
(Literaturubersicht). 

Walz : Baktericide Eigenschaften des Blutes, Braunschweig, 1899. 

Wassermann : Personl. Disposition gegen Diphtheric. Zeitsclir. f. Hyg., xix., 1895. 

Werigo: Les globules blancs comme protecteurs du sang. Ann. de I'lnst. Pasteur, 
vii., 1893; Developp. du charbon chez le lapin, ib., viii., 1894. 

Wyssokowitsch : tSchicksal der ins Blut injic. Mikroorganismen. Zeitschr. f. Hyg., 
i., 1886. 

Ziegler: Ursachen und Wesen der Immunitat des menschlichen Organismus gegen In- 
fectionskrankheiten. Beitr. v. Ziegler, v., 1889; Schutzkrafte des menschlichen 
Organismus. Akad. Rede, Freiburg, 1892 ; Die Lehre von der Entzundung. Beitr. 
V. Ziegler, xii., 1892. 

See also Literature to §§ 31 and 32. 

§ 31. The healing=powers of the human body aj^e furnished hy tJiose 
life-processes ivJiich are able to compensate for the disturbances arid changes 
caused hy disease, and to render harmless or to reinove any harmful agent that 
may still he present in the body. If portions of tissue have been destroyed, the 
healing consists essentially in the removal of the changed and dead tissue, and 
its replacement hy new tissue. 

When from any canse the temperature of the body becomes abnor- 
mally low or abnormally high, compensation may be effected in such 
a way that through the suitable regulation of the heat-production and 
heat- dispersion the temperature of the body may be brought back 
to the normal. If through trauma a portion of tissue is destroyed, the 
organism may repair the defect either through the local production of 
new tissue {regeneration) or by a corresponding increase in other similar 
tissues {compensatory hypertrophy). 

If poisons enter the body and produce symptoms of intoxication, 
healing can follow only through the rapid excretion of the poisou, or its 
destruction or neutralization within the body ; Avhile at the same time the 
damaged tissues, under the influence of normal nutrition, again return 
to their normal state, existing defects being properly compensated. 



HEALING POWERS OF THE BODY IX INFECTIONS. 



109 



In infections healing processes follow directly upon the action of 
the protective forces ; indeed, the action of the latter constitutes the first 
stage of healing; the protective and healing processes are in part identical. 
If the alexins are able to hinder the development of bacteria, and if the 
weakened bacteria are dissolved and destroyed in the tissue-fluids, the 
first step in the healing process will have been accomplished, in that the 
causa efficiens has been removed. If the massing together of cells in the 
infected tissue forms a protecting wall against the spread of bacteria, or 
if the latter are held back in the lymph-glands and there destroyed, such 
phenomena are to be regarded as processes which prepare the way for 
the healing. Phagocytosis may also aid the healing-process. In a similar 
manner the removal of the poisons or the bacteria which have gained entrance 
to the blood through the excretory organs, kidneys, liver, stomach, and 
intestine, not only acts as a protection against the further localization of 
the disease and against increased intoxication, but also makes i30ssible, 
through the removal of the injurious agents, the restoration of the al- 
ready damaged tissues. 

In many infectious diseases the healing influence of protective sub- 
stances already i^resent in the atfected body is supplemented by the ap= 
pearance of new substances foreign to the normal organism, which as 
bactericidal substances and as antitoxins antagonize both the infection 
and the intoxication. These counter -poisons are formed either by the 
tissue -cells and the blood, which through the infection have been i)laced 
under altered conditions of life, or they have been formed by the bac- 
teria themselves ; they spread throughout the tissue- juices, and thus hin- 
der the further extension and multiplication of the bacteria. 

The action of these anti=bodies consists either in the inhibition of 
bacterial growth or the destruction of the bacteria, or in the destruction 
and neutralization of the poisons produced by the bacteria, or in their 
combination with the latter to form inert, non-toxic substances. It is 
also possible (see § 32) that in certain infections they render the tissues 
insusceptible to the bacterial poison. 

The cause of the healing of infectious diseases is most frequently referable to the fact 
that chemical substances exert an antagonistic action against the intoxication, and that the 
bacteria are prevented from further development and so die out. It has been demon- 
strated, however, that in many cases the bacteria may survive and probably also pro- 
duce poisons, which, however, are harmless because of the presence of the antitoxins. 
In individual cases the theory appears admissible that a lack of proper nutritive mate- 
rial causes the death of the bacteria ; as is perhaps the case in localized foci of infection 
(tuberculosis), in which the bacteria, enclosed in dead or slowly degenerating tissue, 
may remain for a long time without being able to escape to new tissues for food mate- 
rial. Further, such changes in the composition of the tissue- juices may be produced 
that the bacteria no longer find the proper conditions of nutrition. Finally, it is also 
conceivable that bacteria, from intrinsic causes within the bacterial cell itself, may no 
longer multiply, and so die out. 

According to the investigations of R. Pfeiffer, which have been confirmed by 
Sohernlieim, Dunbar, Lqffler, and others, the blood-serum of animals rendered immune 
to typhoid-bacilli or cholera-spirilla, or that of human beings ill or convalescing from 
typhoid and cholera, contains, besides antitoxins, also a specific bactericidal substance 
{lysogenous substance of C. Fraenkel). This body possesses the power, when the serum 
is added to a virulent bouillon-culture, so to change the culture that the bacteria, when 
injected into the peritoneal cavity of experimental animals, rapidly break up into mi- 
nute globules and are dissolved. 

According to the investigations of Gruber, BurJiam, Pfeiffer, Kolle, Sober nheim, 
Widal, C. Fraenkel, and others, the blood-serum of individuals ill, convalescing, or en- 
tirely_ recovered from typhoid or cholera, exerts a damaging influence upon typhoid- 
bacilli or cholera-spirilla respectively ; this influence being of such a nature that in 
bouillon-cultures the bacteria so affected become motionless, clump together, sink to 



110 



HEALING POWERS OF THE BODY. 



the bottom of the vessel, aud are destroyed. When the serum is added to a hanging- 
drop of bouillon-culture, the rapidly-moving vibrios at once become motionless and 
collect in little heaps. Gruher believes that this phenomenon is to be explained by a 
swelling and bursting of the membrane of the bacterial cell, and assumes that this 
change enables the alexins to destroy the bacteria present in the body. He therefore 
designates the active substances in the serum as agglutinins, and believes that to these 
may be attributed the chief agency in the healing of infectious diseases and in the pro- 
duction of immunity against the same. Pfeiffer, on the contrary, denies the occurrence 
of an}' swelling of the cell-membrane, and explains the phenomenon as due to an in- 
hibition of development, and dc-iignates the active substances, the nature of which is 
wholl}' unknown, as specific jm i\ihi!si ns. After Grubcr had demonstrated the peculiar 
action of the blood-serum of typhoid-fever patients, Wic^dl {Sem. mkUcale. Paris. 1896) 
proposed that this action of tiie blood-serum on cholera-spirilla aud typhoid-bacilli be 
utilized as a diagnostic aid during the course of an attack of typhoid. The investiga- 
tions of C. Fraenkd, chi Jltis/iil, aud others have demonstrated that it is possible, during 
the course of the attack or for a long time (several monthsi afterward, that the diag- 
nosis of typhoid may be made from the action of the serum upon cultures of typhoid 
bacilli. 

JletscJuu'A'off, Bordet, and others hold that the chief cause of hc^aling from infectious 
diseases and of the acquiring of immunity (see 4; o'.2) is to be found in the activity of the 
leucocytes, which, according to their view, supply bactericidal substances to the body- 
juices and destroy the bacteria by taking them up into their cell-bodies. Phagocytosis, 
however, plays onh' a subordinate role, since most of the bacteria are destroyed by 
the cells, only after they have been injured or killed by the bactericidal substances of 
the blood-serum and the tissue-juices. In many infections bacteria are indeed taken up 
by cells, but are not destroyed by them; on the other hand, they may tiud in the cell- 
protoplasm a soil favorable to their development. 

It has often been assumed that the fever occurring in infectious diseases is a pro- 
tective process favoring the destruction of bacteria; audit is not impossible that in 
individual cases it may exert such a favorable influence. Thus, for example, it is con- 
ceivable that a parasitic micro-organism, growing well at a temperature of 37-38^ C. 
will not thrive at a temperature of 40-41' C., so that high fever-temperatures may hin- 
der its power of reproduction. The conclusion should not. however, be drawn from 
this that fever is a useful phenomenon which always favors the counter-balancing of 
pathological disturbances. Even in those cases in which the metabolic processes occur- 
ring during the fever exert an injurious influence upon the bacteria, this is not to be 
taken as proving the usefulness of fever. We can only say that a part of the morbid 
processes occurring during an infectious fever leads to a formation of decomposition- 
products which may possess antibacterial or antitoxic properties. 



Literature. 

(The Seeding Powers of the 0)r/anism in In feefions and Intoxiecdions.) 

Banti: Sulla distruzzione dei batteri nell' organismo. Arch. p. le Sc. Med., xiii.. 1889. 
Biedl u. Kraus: Ausscheidung d. Mikroorganismen durch Driisen. Zeit. f. Hyg., 
xxvi., 1897. 

Bitter: MetschnikofE's Phagocytenlehre. Zeit. f. Hyg., iv.. 1888; Bakterienfeindl. 

Stotfe thier. Organe, ib.. xii. . 1892. 
Bongers: Ausscheidung korperfremder Stofl'eim ^laa-en. Arcli. f. exp. Path., 35 Bd., 

1895. 

Bordet: Action des serums preventifs. Ann. deblust. Past., 1896; Mc'canisme de Tag- 

glutination, ib., 1899. 
Boucliard: Les microbes pathogenes, Paris. 1892. 
Brieg-er: Antitoxine und Toxine. Zeit. f. Hyg . xxi., 1896. 

Cavazzani: Ausscheidung der Bakterien du^ch die Xiereu. Cbl. f. Bakt.. iv.. 1893. 
Denys et Havel: La part des leucocvtes dans le pouvoir bactericide du sana-. La 
Cellule. X.. 1893. 

Durham: On a Special Action of the Serum. Jouru. of Path., iv.. 1896. 
Eichel: Wachsthumsverhaltnisse verschied. Bakterien im Fieber. ' Virch. Arch., 121 
Bd., 1890. 

Foerster: Die Serodiagnostik d. Abdominaltyphus. Fortschr. d. Med., 1897 (Sam- 
melref.). 

Fraenkel, C: Affa-lutinine bei Tvphus abdom. (Widal'sche Probe). Deut. med. 
Woch., 1897 (Lft.). 



THE ACQUIRING OF IMMUNITY. 



Ill 



Gamaleia: Destruction des microbes dans les organismes febricitants. Ann. de I'lnst. 
Past., 1883. 

Golg-i: II fagocitismo nell' iufezione malarica. Arch. ital. de biol., xi., 1889. 
Gruber: Immuuitat geg. Cholera u. Typhus. Wien. med. Woch., 1896; Theorie der 

Immuu. (Agglutinine). Miinch. med. Woch., 1897; Serumdiagnostik d. Typhus, 

ib. ; Theorie der Agglutination, ib., 1899. 
Hahn: Bezieh. d. Leukocyten z. baktericiden Wirkung d. Blutes. Arch. f. Hyg., 25 

Bd., 1895. 

Jetter: Baktericide Eigensch. d. Blutserums. Arb. a. d. path. Inst, zu Tubingen, 1., 
1893. 

Loewy u. Richter: Heilkraft des Fiebers. Yirch. Arch., 145 Bd., 1896 (Lit.). 
V. Klecki: Ausscheidung d. Bakt. durch d. Nieren. Arch. f. exp. Path., 39 Bd., 1897 
(Lit.). 

Melnikow: Bedeutung der Milz bei Infectionen. Zeit. f. Hyg., xxi., 1896 (Lit.). 
diiMesnil: Gruber- Widal'sche Serumdiagnostik. Miinch. med. Woch., 1897. 
Nissen: Bakterienverniclitende Eigenschaften des Blutes. Cbl. f. Bakt., iv., 1889. 
Pawlowsky: Heilung des Milzbrandes durch Bakterien u. das Verhalten der Milz- 

brandbacillen im Organismus. Virch. Arch., 108 Bd., 1887; Bemerk. lib. d. 

Mittheilung v. Emmerich u. di Mattel : Ueber Yernichtung der JVIilzbrandbacillen 

im Organismus. Fortschr. d. Med., vi. ; Infection u. Immunitat. Zeit. f. Hyg., 

33 Bd., 1900. 

Pernice u. Scagliosi: Ausscheidung d. Bakt. a. d. Organismus. Deut. med. Woch., 
1892 (Lit.). 

Pfeiffer (Kolle, Vag-edes): Ein neues Grundgestz d. Immunitat, etc. Deut. med. 

Woch., 1896: Specitische Immunitatsreaction der Typhusbacillen. Zeit. f. Hyg., 

xxi., 1S96 (Lit.); Weitere Untersuchungen lib. specifische Immunitatsreaction, 

Cbl. f. Bakt., XX., 1896 (Lit.). 
Roger: Elimination des poisons. Path. gen. de Bouchard, 1., Paris, 1895. 
RujBfer: Destruct. des microbes par les cellules amoeboides. Ann. de ITnst. Past., v., 

1891. 

Sherrington: Exper. on the Escape of Bacteria with the Secretions. Journ. of Path.,, 
i., 1893 (Lit.). 

Sirotinin: Entwickelungshemmende Producte der Bakterien. Zeit. f. Hyg., iv., 1888. 

Tsuboi: Die Schutz- und Heilsubstanz des Blutes, Wiesbaden, 1892. 

Wassermann : Pneuraokokkenschutzstotfe. Deut. med. Woch., 1899. 

Widal et Sicard: Le serodiagnostic. Ann. de I'lnst. Past., 1897 (Lit.). 

Ziegler: Die Ursachen d. pathol. Gewebsneubildungen. Internat. Beitr., ii., Festr. f. 

Yirchow, Berlin, 1891 ; Ueb. d. Zweckmassigk. d. pathol. Lebensvorgange^ 

Miinch. med. Woch., 1896. 
See also § 30 and § 32. 



II. The Acquiring of Immunity against Infection and Intoxication^ 
Protection through Inoculation. 

§ 32. The acquiring of immunity against a particular infectious 
disease is a phenomenon whose freqnent occurrence has long been known 
through clinical observations. This fact has been established chiefly by 
the observation that the great majority of men suffer but one attack of 
such widespread infections as measles, smallj)Ox, whooping-cough, scar- 
let fever, and diphtheria, and that after such attack they are spared by 
the disease, even when they expose themselves under the most varied 
conditions to the danger of infection with its poison. The knowledge of 
this fact is very old, and early in the eighteenth century it had led, in 
the Orient, to attempts to obtain immunity against the natural contagion 
of smallpox by the inoculation of material from smallpox pustules. In 
the latter part of the eighteenth century Jenner discovered that the dis- 
ease known as cowpox — i.e., a milder form of pox, which is either a 
special variety of disease closely allied to human smallpox or a weaker 
form of the latter— afforded protection against the true smallpox. As 
a result of this observation, since the beginning of the year 1796, at first 
by Jenner himself, afterward by the physicians of all civilized countries, 



112 



THE PROTECTIVE FORCES AGAINST INFECTION. 



artificial iuocnlations of cowpox have been carried out upon millions of 
hnniau individuals, with the result that through such inoculation a high 
degree of immunity against the true smallpox has been secured to the 
inoculated; so that at the present time, in all countries where vaccina- 
tion is universally practised, the occurrence of widespread epidemics of 
smalli)ox, once so frequent, is very rare, and the disease no longer as- 
sumes the character of a dangerous pestilence. 

The investigations of the last decades with regard to the causes and 
origin of infectious diseases, which have covered such an extraoi dinarily 
broad field, have shown that the acquiring of immunity against a cer= 
tain infectious disease through one attack of the given disease oc- 
curs in different infectious diseases, especially in those running an acute 
course; and represents sometimes a transitory, at other times a i^ev- 
manent peculiarity of the individual concerned, which in pregnant 
women may be transmitted to the foetus in idero. These observations 
have also shown that the single or repeated Inoculation of attenuated 
pathogenic bacteria — that is, of bacteria which on account of their slight 
virulence produce a disease that, in contrast to the natural infection with 
bacteria of full virulence, is relatively insignificant, often localized to a 
limited area — can also confer immunity against the corresponding dis- 
ease. Further, it has been demonstrated that the injection of certain 
chemical substances produced by the bacteria is sufficient to confer 
iinmunitj^ against certain infections. 

In explanation of the immunity accpiired through an infectious 
disease or through inoculation, we are at the present time limited to 
hypotheses, yet it cannot be doubted that the last few years have brought 
great advance in our knowledge of the forces concerned in the produc- 
tion of such immunity, so that we at least know in what direction 
further researches should be made. 

After Pasteur had, in 1880, proved experimentally that chickens 
€Ould be made immune against chicken- cholera through injections of 
attenuated chicken -cholera poison, and after it had been established by 
the investigations of different authors that similar results could be ob- 
tained in anthrax, symptomatic anthrax, and swine-erysipelas, it was at 
first believed that the acquiring of immunity could be explained by the 
fact that through the inoculation or the first attack of the given infection 
the food-material in the body had been exhausted (Pasteur, Klebs), so 
that bacteria entering the body later were unable to find food. This 
hypothesis, known as the exJimistion -theory, cannot be brought into har- 
mony with the observed facts, so that it is now generally abandoned. 
Also the view of Metschnikoff, that the mesodermal cells become accus- 
tomed through the preventive inoculations, to the taking-up of the pre- 
viously untouched virulent bacteria, and quickly take them up and 
destroy them after repeated inoculation, can in no wise be regarded as 
an hyi^othesis based upon scientific foundations. 

According to the facts which have been ascertained by investigations 
concerning the natural protective powers of the body against infection, 
and the natural mode of recovery from infections, as well as the experi- 
ments made with regard to protective inoculation and the artificial heal- 
ing of infectious diseases, it is very probable that acquired immunity 
is dependent upon the presence of certain chemical substances which 
are either poisonous for the particular variety of bacteria concerned, or in 
some mamier or other counteract the activity of the product formed hy these 
bacteria (poison- theory). It is yet an unsettled question whether these 



THE ACQUIRING OF IMMUNITY: THE POISON THEORY. 



113 



substances are pro'liiets of the body-cells ; further, Avhether the loss of 
toxic actiou of the toxalbuimns and toxins formed by the bacteria is due 
to a destruction of the same, or to the formation of inert combinations 
of these bodies, or to an immunization of the body-cells against these 
poisons. 

Some light with regard to these questions is given by our present 
knowledge concerning the different ways in which, not only in experi- 
mental animals, but also to a certain extent in man, an immunity against 
certain infectious diseases may be obtained. Further light is also ob- 
tained from experiments concerning the artificial healing of infections 
which have already begun to develop. As previously stated, it is ];)ossible 
to x^roduce in animals, in harmony with the knowledge obtained through 
Jenner's cowpox inoculation, an immunity through the inoculation 
of attenuated specific disease=germs ; as, for exami)le, in anthrax, 
symptomatic anthrax, chicken-cholera, diphtheria, swine- erysipelas. 

The weakening of the virulence of bacteria may be produced either 
by the action of high temperatures or chemical agents, or by the action 
of the air alone ; further, it may also be produced by the inoculation of 
the bacteria into certain animals or through their long-continued culti- 
vation on artificial media. Inoculation is, in general, carried out by in- 
jecting subcutaneously first markedly attenuated, then less attenuated, 
and finally fully virulent bacteria together with their products. 

According to the investigations of numerous authors, immunity in 
animals may also be produced by the injection of sterilized cultures 
in which the bacteria are completely killed — as, for example, against 
American hog-cholera, symptomatic anthrax, di]3htheria, the infectious 
disease produced experimentally in rabbits by the injection of the 
Bacillus pijocyaneus, and the infection produced in guinea-pigs by cholera- 
spirilla. It is probable that the immunizing substances are contained 
in the cell-substance of the bacteria (Brieger, Kitasato, Wassermanu). 

A third form of artificial immunization, which Raynaud attempted 
as early as 1877 but was first securely established by Behring in 1890, 
can be produced by the injection into man or an experimental animal of 
blood-serum taken from animals which were previously susceptible, 
but have been rendered immune by means of inoculations. The most 
extensive and at the same time the most successful attempts thus far 
made have been carried out with diphtheria and tetanus ; that is, in dis- 
eases in which intoxication through toxalbumins forms the most striking 
feature. Moreover, successfal experiments with the blood-serum of 
immunized animals, in the case of cholera, swine -erysipelas, anthrax, 
typhoid fever, and plague, have been reported. 

The specific protection which the blood-serum affords may be secured, 
not only by injection before infection occurs, but also after infection 
has already taken place; so that the serum may be designated not only a 
protective serum, but also a healing serum. For both protection 
against and for the cure of a certain infection a definite amount of serum 
is necessary, the precise amount depending, on one hand, upon the se- 
verity of the infection, and On the other, upon the activity of the serum 
itself, which increases with the completeness of the immunization of the 
originally susceptible animal furnishing the serum. If the serum is not 
injected until after infection has occurred, the amount of serum must be 
so much the greater the longer the lapse of time after the beginning of 
the infection. 

In the case of true bacillary diphtheria, the injection of curative 
8 



114 



THE PROTECTIVE FORCES AGAINST INFECTION. 



diphtheria- serum has no^y been carried out in thousands of cases, of 
both sevei'e and light forms ; and there is without any doubt a beneficial 
intiuence exerted upon the course of the disease, as shown by a rapid 
improvement of the j)atient's general condition (rapid establishment of 
euphoria, fall of fever, improvement in the pulse), as well as by the 
favorable course i^ursued by the local disease. In tetanus a definite cur- 
ative action of serum has been demonstrated in the case of experimental 
animals, guinea-pigs, and mice; but the results in man have not yet been 
fullj' determined. 

The blood-serum of immunized animals exerts its beneticial action, 
without doubt, through the presence of a cQunter-i)oisoii, an antitoxin, 
which neutralizes the poisons produced by the bacteria. In the case of 
the patients treated by a given antitoxin, there is produced a poison= 
immunity against the corresponding bacterial i^oison — as, for example, 
against the poison produced by the diphtheria bacilli, in those patients 
injected with diphtheria -antitoxin — and this immunity is to be ascribed 
to the presence of a definite amount of antitoxin in the blood. 

The chemical nature cf the antitoxins, whose occurrence in numerous 
infections and intoxications (diphtheria, tetanus, pneumonia, snake- 
poison, poisoning with ricin, abrin) has been demonstrated, is not 
known. Their mode of action may be explained either by the assump- 
tion that they destroy the specific bacterial poisons (Behring), or that 
they only render the tissues insusceptible to the action of the latter 
(Buchner, Tizzoni, and others), or finally, that they form in the blood 
and tissue- juices a chemical combination with the toxins which is not 
harmful to the cells (Ehrlich). 

Besides the antitoxins, the blood-serum of immunized animals or 
human beings may also contain bactericidal substances, which injure 
or kill the bacteria themselves ; and this is said to occur especially in 
cholera and typhoid infections (E. Pfeiffer, Gruber, Durham) and in in- 
fections with the j)neumococcus (Emmerich). Emmerich assumes that 
these substances are of the nature of bacteriolytic enzymes. 

The origin of the immunizing substances in the blood is not j^et 
known, and we are at present confined to hypotheses. It is probable 
that the bactericidal substances have not the same genesis as the anti- 
toxic. 

In the case of immunization by means of attenuated cultures or by 
sterilized chemical bacterial products, the antitoxic substance is pro- 
duced as a new body within the organism, and this process has been 
designated active immunization (Ehrlich) ; in the case of the injection 
of immunizing serum the antitoxin already formed is introduced from 
without, and this may be spoken of as passive immunization. It is 
probable that in the last case no new-formation of antitoxin occurs after 
the injection. 

It is most probable that antitoxins are formed bij the cells of the infected 
individual, according to Ehrlich's view (see below) by those cells which 
are especiallj" influenced by the toxin (in tetanus, for example, by the 
nerve-cells). The antitoxin is probably nothing more than an element 
of the cell-protoi)lasm, which has an especial relation to the given toxin, 
and, thrown off from the cell and dissolved in the blood, combines with 
the toxin to form a harmless body. The fact that the substance produc- 
ing the immunity is active only against the given infection may be ex- 
plained by the assumption that the individual toxins or toxalbumins 
possess the atfinity, which is necessary to the production of an intoxica- 



THE ACQUIRING OF IMMUNITY: PROTECTIVE INOCULATION. 115 



tion, only for certain x^ortions of certain cells; and that, therefore, 
following the intoxication, only the immunizing substances for the par- 
ticular poison are produced by the cells and given to the blood. 

By many Avriters it is believed that the anti-bodies, both bactericidal 
substances and antitoxins, are formed by the bacteria themselves, or that 
the bacterial cells furnish the material for these, in cultures as well as 
within an infected body (Buchner). 

For the foundation researches in regard to inoculation with attenuated cultures of 
bacilli cultivated outside of the body, we are indebted to Pasteur, who, in 1880, demon- 
strated the fact that chickens could be immunized against chicken-cholera through the 
inoculation of cultures of cidcken-cholera hacilU, that had been weakened through long 
exposure to the air. 

Since that time numerous experiments have been carried out with other forms of 
bacteria, especially with attenuated cultures of the bacilli of anthrax and symptomatic 
anthrax. The best results have been obtained from inoculations against the symp- 
tomatic anthrax of cattle. Less favorable are the results in inoculations against an- 
thrax, in that some of the animals die from the effects of the protective inoculation, 
while others are not rendered absolutely immune against a new anthrax infection. 

Sheep and cattle may be made immune against (f ntlrnt.c ; most expediently {Koch) 
by first inoculating them with attenuated cultures of antlirax-bacilli, which will kill 
mice but not guinea-pigs, and then with those which Avill kill guinea-pigs but not 
strong rabbits. 

As vaccine against symftomatic anthrax, there may be used cultures of the bacillus 
attenuated through heat or such chemical agents as sublimate solutions, thymol, 
eucalyptol, and silver nitrate ; and by such inoculations cattle may be rendered im- 
mune. At the present time heat {Hess, Kitt) is most commonly used in the prepai-ation 
of the vaccine. The infected muscle of an animal dying with symptomatic anthrax is 
chopped fine, triturated with one half its weight of water, and pressed through a piece 
of linen cloth. Finally, the fluid is again filtered through a moistened piece of fine 
linen. The virulent material is then spread in thin layers upon glass plates or flat 
dishes, and transferred to a dry chamber at a temperature of 82-35° C. When thor- 
oughly dry the virus is scraped off and removed in the form of powder. When it is 
desired to give inoculations, the virus is triturated with double its weight of water and 
the fluid evaporated in a thermostat. By raising the temperature to 100° C. for six 
hours a weak vaccine is obtained ; at a temperature of 85° C. for six hours a stronger 
one. For the immunization of cattle, about 0.5 gm. of the weaker virus in a dilute 
water solution is injected into the subcutaneous tissue of the animal's tail, and after 
eight to twelve days the stronger solution is similarly injected. 

According to observations of Chanvea,u and others, protective inoculations may also 
be made by the injection of virulent bacteria in very small quantities, or in such a 
manner that the life of the animal shall not be endangered. In the case of sympto- 
matic anthrax this may be accomplished by the injection of very small doses into the 
extremity of the animal's tail; such injections not causing a fatal illness, but only a 
local disturbance. 

According to Afanassieff, it is possible to render animals immune by inoculating 
the granulating siu-face of a wound with a virulent culture. 

Cattle may also be immunized against contagious pleuropneumonia {Schiitz) by in- 
jecting the tissue-juices from the lung of an animal d3'iug from this disease into the 
ibip of the tail. Tliere is produced in this w^ay a- circumscribed inflammation, or, at 
least, one which is confined to the tail ; after recovery from which the animal is im- 
mune to both natural and artificial infection with this disease. 

Hogs may be rendered immune against inoculation with virulent bacilli of swine- 
erysipelas {Pasteur), by using, as vaccine, cultures attenuated b}^ successive inocula- 
tions in rabbits. According to Emmerich, rabbits may also be made immune against 
the bacilli of swine-erysipelas through the injection into the ear-vein of a small quan- 
tity of a virulent bouillon-culture diluted with fifty times its volume of water. 

Animals susceptible to diphtheria may be rendered immune against this disease, 
according to Bchring, by the injection of cultures of diphtheria-bacitli which have been 
weakened in virulence by exposure for sixteen hours to iodine trichloride (1 : 500). Two 
cubic centimetres of such a culture is injected into the peritoneal cavity; after three 
weeks this injection is repeated with a diphtheria-culture (0.2 c.c.) which has been 
washed four days in bouillon containing iodine trichloride (1 : 5,500). After this, fully - 
virulent cultures are injected in increasing doses. 

Rabbits may be rendered immune against pn^umococci {Emmerich) by injections 



116 THE PROTECTIVE FORCES AGAINST INFECTION. 



of 0.3 c.c. of a strongly-virulent bouillon-culture which has been diluted five thousand 
times, followed later by injections of bouillon-cultures of full virulence. 

Protective inoculalions against rabies were tii'st carried out in cases resulting from 
bites b3Mabid animals, particularly in France (Pasteur Institute), Russia, and Italy. 
As inoculation-material, the spinal cord from rabbits which have been infected with 
rabies is used after it has been di'ied in dry air at a temperature of 28-25" C. ; the viini- 
lency of the cord being gradually lost after about tifteen days of the drying-process. 
According to Pi-otopopoff, it is the temperature, and not the drying {Padear), which 
lessens the \ irulence. According to Marx, the micro-organisms of rabies have already 
been weakened in the body of the rabbit. Small portions of a rabbit's cord thus weak- 
ened in virulence are triturated in sterilized chicken-broth and injected subcutaneously 
into the bitten individual; at first pieces of cord greatly reduced in virulence are used, 
then those of gradually increasing virulence. According to the view held by Pasteur, 
the spinal cord contains both the microbes of the disease and the specific poison formed 
by them; if the latter spreads through the body more rapidly than the microbes, it con- 
fers an immunity against a subsequent spread of the microbes, and affords protection 
to the nervous system in particular. In order to confer immunity it is, therefore, 
necessary to introduce as large a quantity as possible of the chemical poison. Accord- 
ing to the reports of the Institutes in which the Pasteur inoculations against hydro- 
phobia have been carried out, it must be acknowledged that these inoculations have 
been successful in preventing cases of hydrophobia. 

Immunity against cholera may be produced, in both man and animals {Haffkine, 
Pfeiffer, Kolle, Voges, and others), b}^ the injection of sterilized or attenuated cultures 
of cholera-spirilla; this immunity (which is of short duration) depends upon the forma- 
tion of specific bactericidal anti-bodies in the blood (see Voges, 1. c). On the other hand, 
we do not yet possess a specific remedy by which the life of any animal or man in- 
fected with cliolera ma}^ be saved. 

Immunity against typhoid fecer ma}' be secured in man by the subcutaneous injec- 
tion of sterilized cultures of t^'phoid-bacilli {Pfeiffer, Kolle) ; and the establishment of 
the inmiunity ma}' be recognized by the fact that the blood-serum of the individual so 
inoculated is found, after a few days, to contain bactericidal substances. Attempts at 
immunization in cases already ill with typhoid {Brieger, Wassermann, C. Fraenkel) 
have up to the present time been unsuccessful. 

According to the reports published hy Koch {British Medical Journal, 1897; Deut. 
med. Wochen., 1897, No. 16; Centndbatt f. Biilt., xxi., p. 526) of the investigations 
which were carried out during the winter of 1896-1897 with regard to the cattle-plague 
in Cape Colony, cattle may be immunized ngSLm^it Binder jjest^^ by subcutaneous in- 
jections of 10 c.c. of the bile taken from animals dying of the disease; the condition of 
immunity becoming established at the latest by the tenth day. According to the re- 
port of Professor Winkler (" Landwirthschaftl. Bezirks-Verein Giessen," August, 1900) 
hogs and cattle may be immunized against motith-and-hoof disease through feeding with 
milk of animals which are affected by the disease or have recently recovered from it. 

In the year 1890 Koch made the discovery that cultures of tubercle-bacilli contain 
a toxin, tuberculin,^'' which, when injected into tuberculous individuals, causes a rise 
of temperature and to some extent local inflammatory changes in the neighborhood of 
tuberculous foci. It was at first hoped that in tuberculin a remedy for tuberculosis had 
been found, but the many trials made with it upon human beings and animals have 
shown that it indeed produces after repeated injections an immunity against the toxic 
action of tuberculin but does not hinder the multiplication of tubercle-bacilli and the 
consequent spread of the disease. Further, the local inflammation caused by the tuber- 
culin leads to favorable results only imder special conditions, but, on the other hand, 
often causes actual harm (through the metastasis of bacilli). Nevertheless, Koch's dis- 
covery has proved of great importance. In the first place, it is of practical value in 
the diagnosis of tuberculosis, in that tuberculin injections do not excite fever in normal 
individuals. Inoculations for diagnostic purposes are now used very extensively in 
cases of suspected tuberculosis in domestic animals. Moreover, the reports published 
by Koch gave a great stimulus to further investigations with regard to immunization 
by means of inoculation with bacterial toxins; and these investigations have led t(^ the 
discovery of the antitoxins of diphtheria, tetanus, cholera, and typhoid fever. 

Maragliano has recently attempted to obtain a healing-serum against tuberculosis 
by the inoculation of experimental animals (donkey, dog, horse) with the toxins de- 
rived from cultures of tubercle-bacilli. The observations thus far made do not war- 
rant the conclusion that this serum possesses the power to cure tuberculosis in the 
human being. In 1897, Koch ("Ueber neue Tuberculinpraparate," Beut. med. Woch., 
1897) succeeded in obtaining from highly virulent cultures of tubercle-bacilli a substance 
which he claims is able to immunize against all of the constituents of the tubercle- 
bacillus. To obtain this substance young cultures of tubercle-bacilli are dried in a 



THE ACQUIRING OF IMMUNITY: EHRLICH'S HYPOTHESIS. 117 



vacuuni-exsiccator and then triturated. The product obtained b}' trituration is mixed 
with distilled water and ceiitrif ugated. The active substance is contained in the muddy 
precipitate thus obtained (designated by Koch as T. R.). This is again dried and tritu- 
rated, dissolved in water to which twenty per cent of glycerin is added for the purpose 
of preservation. (The preparation is manufactured b}' Meister, Lucius, and Briiiining, 
at Hochst-on-the-Main, Germany.) The fluid preparation contains 10 mgm. of solid 
substance in every cubic centimetre, and when it is to be used should be diluted with 
physiological salt solution. Through the use of large doses animals are said to become 
immunized in from two to three weeks. In the treatment of tuberculosis in man the 
dose should begin at ]ngm. and gradually be increased up to 20 mgm., the injections 
being given every other day. According to the observations so far published, the T. R. 
preparation does not appear to exert a curative action upon tuberculosis in man. " 

Very recently Tube has reported that there may be obtained from cultures of 
tubercle- bacilli a substance (tuberculo-bactericidin) wdiich has a bactericidal action; but 
no detinite conclusions can be drawn from the published results of his experiments. 

The blood-serum treatment of cliphtJieria, i.e., the employment of the antitoxins con- 
tained in the blood of an animal immunized against diphtheria as a means of curing 
that disease when it is already contracted, or as a protection against such infection, is 
a discovery which we owe to Beliring. The favorable effects of the method discov- 
ered and proved by him through experimental investigations have been confirmed by 
thousands of observations. In the treatment of diphtheria patients a large quantit}^ of 
the serum (one thousand immunizing units) is usually injected at one time beneath the 
skin of the thigh. 

The term " normal serum " — i.e., a serum having the value of one immunization 
unit — is used by Beliring to designate a serum which, when mixed with a quantity of 
diphtheria poison equal to ten times the minimal fatal dose and then injected in the 
amount of 0.1 c.c. into a guinea-pig of from 200 to 30u gm. weight, will surely protect 
that animal from diphtheria. Sheep and horses are especially aclapted for the prepara- 
tion of the serum. It is prepared and sold in doses of from live hundred to three thou- 
sand immunization units. 

If culture-filtrates of the ^d7'(/////.v-/A^r/////,v are weakened by the action of chemical 
agents (iodine trichloride or iodine combined with potassium iodide), it is possible 
through repeated injections of such filtrates of increasing virulence to produce im- 
munity in animals against tetanus {Kitasato, Beliring, Tinoni, Bn rimer). The blood of 
such immunized animals contiims an antitoxin tohich aTfords a sure ijrotection to experi- 
mental animals against tetanus. The antitoxin treatment of human beings suffering 
from tetanus has not given satisfactory results (see Kolder and Scldesiuger, I.e.), not 
even in cases of relatively early injection of the antitoxin, though it appears to be 
effective if administered before the appearance of the tetanus. 

Susceptible animals and human beings may be immunized against hubonictplague 
by means of sterilized cultures of the pest-bacillus {Yersin, Haffldne. Kolle); and it ap- 
pears that in the blood-serum of immunized animals (the horse, for example) there are 
present anti-bodies which render the serinu utilizable for both protective and curative 
purposes. 

Animals may be made immune against snake-poisons by means of inoculations of 
very small doses of such poison continued for some length of time {Ccdmette, Tschisto- 
witsch); and the blood-serum of such immunized animals is also found to possess an 
antitoxic action against the given poison, so that it may be used as a healing-serum. 
In Brazil, Mexico, Africa, etc., various methods involving the use of snake-poison 
itself are employed for the immunization of individuals against a snake-bite, or for 
curing them after they have been bitten (drinking of the secretions of the poison- 
glands, rubbing of the diluted poison into small wounds of the skin, etc.) {Brenning). 

According lo the investigations by Ehrlich, mice may be made immune against 
ricin, to which they are extremely susceptible, by mixing very small doses of ricin 
with their food and then afterward injecting additional small doses subcutanoously. 
The appearance of the immunity occurs on the sixth day after the administration of the 
ricin, so that upon this day the animal can withstand a'^dose thirteen times as great as 
at the beginning. Through continued S3^stematic inoculations the animal becomes 
immune to a dose eight hundiedfold as strong. The immunity is produced by an anti- 
toxic body, antiricin, which neutralizes the poisonous action of ricin. 

Though not giving definite information regarding the processes which lead to the 
acquiring of immunity, the hypotheses of Ehrlich are well qualified to give an explana- 
tion for the observed processes, and possibly correspond to the actual conditions. 

According to EhrliclVs view, only those substances are poisons which possess a 
chemical relationship with some constituent of the body, and, through combination 
with the same, cause an injurious effect recognizable cliuicall}^ (toxophorous relation- 
ship). The natural immunity of an individual can, therefore, depend upon the fact 



118 



THE PROTECTIVE FORCES AGAINST INFECTION. 



that the poison finds in the immune body no element with which it can effect a chem- 
ical combination, or that the body-element so combined suffers no injury in a clinical 
sense. 

Antitoxic immunity can be produced either through the introduction of weak doses 
of toxin or through the injection of a serum containing antitoxin. T^-he first is an ac- 
tive immunization, in that the organism itself forms the toxin ; the second is a passive 
immunization, in that the antitoxin is injected already prepared, so that immunity is at 
once produced. The active immunity can persist for years ; the passive, on the con- 
trary, is usually lost after a few weeks or months at the farthest. 

An antitoxin is a cell-product w^liicli arises as a result of disease of the organism, 
and is given off into the blood. In passive immunity the body-cells are not active, the 
injected antitoxin is sufficient to neutralize the toxin. Antiricin, when added in a cer- 
tain amount to a ricin-solution, lowers the power of ricin to agglutinate red blood-cells 
in undiluted or in diluted blood. The same mixture also renders ricin harmless for 
animals. 

The toxin is not destroi/ed hy the antitoxin. If snake-venom he mixed with the 2inx\- 
toxin (Calniette), so that the mixture is harmless for animals, and if the antitoxin, which 
is the more sensitive to heat, be destroyed by warming the mixture to 68" C, this again 
becomes poisonous. A similar fact has been demonstrated in the case of the toxin aD^i 
antitoxin of the Bacillus pyocyaneus ( Wassermann) . 

The toxin becomes harmless tliro^i'jh its union with the antitoxin to form a harmless 
chemical combination. 

The antitoxin produced in the body in cases of active immunization does not arise 
from the toxin. The poisons forming antitoxins show, in contrast to other poisons, 
certain peculiarities, which consist essentially in that they possess chemical atfinities 
for certain elements of the cells, the "side-chains." The complicated protoplasmic 
bodies possess (as does the benzol ring), besides the '"''governing nucleus'''' or ^''central 
group,'''' a great variety of such "'side-chains.''^ It maj^ be assumed that certain sub- 
stances influence certain side-chains, enter into chemical combination with the same, 
and through the medium of these side-chains affect the central chain and thereby dam- 
age the vital capacity of the cells. If thereby the life of the cell and with this its 
capacity for compensation are not damaged, if there occurs only a functional disturb- 
ance but no definite injury to the central group, the cells may restore the side-chains, 
even build up new ones in excess, which may be thrown off and given to the blood, 
the side-chains thus given off constituting the antitoxin. The antitoxin is therefore no 
new substance, but one occurring normally, which under certain conditions is pro- 
duced in an increased amount, given over to 'ilie blood, and in the circulation combines the 
toxins entering the blood into harmless bodies, and thus prevents the action of the 
toxins upon the cells. x\.s expressed in the words of Behring: "The same substance in 
the living body, which Ijing in the cells is the hypothetical essential to an intoxica- 
tion, becomes the cause of healing when it is found in the blood." 

Ehriich's hypothesis is without doubt well adapted to explain the phenomena of 
antitoxic immunity. It has been supported by recent observations of different authors, 
Wassermann has found that the substance of the central nervous system which is espe- 
cially affected in tetanus is able to combine the tetanus poison after the manner of an 
antitoxin and to render it harmless. Tetanus-poison, when mixed with the triturated 
brain-substance of a healthy guinea-pig, becomes so w^eakened that guinea-pigs can 
bear without harm a dose equal to ten times the fatal dose. 

Ransom and Marie obtained the same results. The former also showed that the 
poison of tetanus, wnen injected in fatal doses into doves, could be demonstrated in all 
organs with the exception of the central nervous system, in which it had entered into 
combination with chemical elements. 

Ehriich's h3^pothesis has been attacked especially by Roux, Borrel, Metschnikoff, 
and Knorr ; but their observations may be brought into harmony with the hypothesis 
(see Weigert, I.e.). 

Bactericidal immunity depends chiefly upon the presence of newly-formed immune- 
bodies, which are able to withstand heating to 56-60° C, and. wholly specific in their 
action, are directed against the variety of bacteria corresponding to the immunization 
{R. Bfeiffer and others). 

These immune bodies exert their influence under certain conditions ; according to 
the view held by Bordet, Ehrlich and Morgerroth, von Dungern, and Wassermann, their 
activity is dependent upon the addition of a tbermolabile ferment-like substance, which 
is found even in normal blood-serum (according to Bordet, the alexin of Buchner, the 
Oiddiment or complement of Ehrlich). 

Of exactly the same composition as the bactericidal are also the corresponding 
globulicidal immune-sera (specific hceniolysins), which are produced by the introduction 
of blood into the body of an animal of a different species {Bordet, von Dungern, Land- 



THEORY OF SPECIFIC IMMUNE-SERA. 



119 



■ffteiner); in this case also the action of the immane-serum depends upon the presence of 
two substances — the immune-body produced through the immunization, and the comple- 
ment ah-eady present in normal blood-serum. Eltrlich and Morgenroth have further 
explained the mechanism of these processes by means of experiments at combining 
these substances. The immune-body shows great specific affinity for the correspond- 
ing erythroc3'tes; it combines with these even at 0° C, and, thus separated from the 
complement remaining in the serum, is nevertheless not able to dissolve the blood- 
corpuscles by itself. The complement will not be combined by the blood-cells without 
the immune-body. If the latter is present at the same time, the complement is taken 
at higher temperatures out of the serum by the erythrocytes, whereby the solution of 
the red cells takes place. 

Ehrlich and Morgenroth explain this by the assumption that the complement, which 
represents the active substance proper, is carried over to the erythrocytes by means of the 
immune-body. This conclusion accords very well with the side-chain theory. The im- 
mune-body is a side-chain, which, produced in excess, is thrown off into the blood. To 
the production of the im.mune-body a certain molecule-group of the erythrocytes gives 
occasion, and this group is indeed the same which in haemolysis enters into combination 
with the immune-body {ton Dungern). The immune-bodies are distinguished from the 
analogous antitoxins only in that they are more complex ; they possess, besides the 
haptophorous complex which has a chemical affinity for the corresponding complex of 
the proper erythrocytes, yet another haptophorous groujD, which is able to combiDC the 
complement. Corresponding complementophile side-chains may also be demonstrated 
in the organs ; the most varied kinds of tissue-cells are able to take out the complement 
from the blood-serum {von Dungern). 

In the reaction of immunity the immune-bodies are produced exclusively ; the com- 
plement is not increased beyond the amount required {von Dungern). 

The property of many normal sera to dissolve foreign blood-cells is dependent, ac- 
cording to the investigations of Ehrlich and Morgenroth, exactly as in the case of the 
immune-sera, upon the joint action of two substances. Many times there can also be 
demonstrated, besides the complement, an "intermediary body" corresponding to the 
immune-body (the complement is therefore not wdiolly to be identified as Buchnefs 
alexin, which embraces both substances). 

In an analogous manner to that produced against bacteria and red blood -cells, a re- 
action of immunity may occur against other cells when introduced into a strange 
organism — for example, against ciliated epithelial cells {ron Dungern), against sperma- 
tozoa {Landsteiner, Metschnikoff, Moxter), against leucocytes {Metschnikoff and others). 
The immune-sera obtained in this manner act, in so far as they have been studied iron 
Dungern, Moxter), according to the same mechanism as the haemolytic and bactericidal. 

The reaction, of the animal organism, ichich hinders or makes impossible the life of cells 
foreign to it, is manifested not only tipon bacteriabut upon all possible forms oj life foreign 
to it. According to the investigations of Ehrlich and Morgenroth, the same reaction 
may occur even against blood-cells of the same species. After intraperitoneal injection 
of laked blood of the same species, the blood-serum of a given species acquires the 
power to dissolve the red blood-cells of another individual of the same species (isolysin). 
An autolysin has, on the other hand, not yet been observed. The latter could indeed 
not exist in the blood ; it would be combined with the corresponding side-chains of the 
cells (receptors) and occasion the production of an antiautolysin. 

The acquired specific immunity against the causes of infection is, therefore, to be 
referred to the general law of the formation of anti-bodies. 



Literature. 

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xxii., 1897. 

Arloing, Cornevin, et Thomas: Le cliarbon symptomatique, Paris, 1887. 

Babes: Studien iiber die Wuthkrankheit. Virch. Arch., 110 Bd., 1887. 

Baumgarten : Phagocytenlehre. Beitr. v. Ziegler, vii., 1890; Jahresber., 1891-98. 

Beck: Untersuchungen liber Tetanus. Zeit. f.^Hyg., xix., 1895. 

Beclere, Chambon et Menard: Immunite vaccinale. Ann. de I'lnst. Past., 1896. 

Behring-: Die Ursachen der Immunitat von Ratten gegen Milzbraud. Cent. f. klin. 
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ib., xii., 1892; Die Geschichte der Diphtheric, 1893; Gesamm. Abhandlungen z. 



120 



THE PROTECTIVE FORCES AGAINST INFECTION. 



atiol. Tlierapie, Leipzig, 1893; Infection u. Desinfcction, Leipzig, 1894; Leistungen 

u. Ziele der SerumUieiapie Dent. med. Woch., 1895; Immunitat. Eiilenburg's 

T\ealencj4ilop., 1896 ; Antitoxintherapeutische Probleme. Fortschr. d. Med.. 1897; 

IIeili)riucipien. Deut. med. Wocli., 1898. 
Bitter: Yerbreitung d. Yaccins n. d. Impfsclmtzes im Korper. Zeit. f. Hyg., iv., 

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gegeu Pest, ib., xxx., 1899. 
Bonome: Transfusion von Blut u. Serum immuuis. Tliiere. Fortschr. d. ]\Ied., ix., 

1^91. 

Bordet: Serum antistreptococcique. Ann. de I'lnst. Past., 1897. 
Brenning": Die Yergiftungen durcli Schlangen, Stuttgart, 1895. 

Brieger, Kitasato u. Wassermann : Immunitat und Giftfestigung. Zeit. f. ITvg., 
xii., 1892. 

Brieger u. Ehrlich.: Die Milch immunisirter, Thiere. Zeit. f. H^'g., xiii. 1893. 
Bucliner: Immunitat u. Immunisirung. Munch, med. Woch., 1889, 1897, 1899; 

Bakteriengifte u. Gegengifte, lb., 1893; Schutzimpfung. Handb. d. spec. Ther., 

i.. Jena, 1894. 

Calmette: Yenins, toxines et antitoxines. Ann. de Tlnst. Past., 1895; Yenins des ser- 
pents et seriun antivenimeux, ib., 1897. 

Calmus et Gley: Immunite contre le serum d'anguille. Ann. de I'lnst. Past., 1899. 

Charrin: L'immunite. Arch, de phys., v., 1893; Traite de path, gen., ii., Paris, 
1896. 

Cliauveau: Tlieorie des inoculations preventives. Rev. de med., 1887; Mecanisme 
de rimmunite. Ann. de I'lnst. Past., ii., 1888; Proprietes vaccinales des microbes 
ci-devant pathogenes transformes en microbes d'apparence saprogene. A. denied, 
ex p., 1.. 1889. 

Corbette: The Action of Antitoxins. Journ. of Path., vi., 1899. 

Delius u. Kolle: Influenzaimmunitat (lasst sich nicht erzielen). Zeit. f. Hvg., 24 Bd., 
1897. 

Deutsch: Origine des anticorps typhiques. Ann. de I'lnst. Past., 1899. 
Dieudonne: Schutzimpfung u. Serumtherapie, Leipzig, 1895. 

Ehrlich: Ueber Ricin u. Antiriciu. Deut. med. AVoch., 1891; Fortschr. d. Med.. xv., 
1897: Die Werthbemessung d. Diphtherieheilserums. Klin. Jahr., 1897; Immu- 
nitat durch Yererbung u. Siiugung. Zeit. f. H^'g., xii., 1892; Zur Keuntniss d. 
Antitoxinwirkung. Fortschr. d. Med., 1897. 

Emmerich: Ursaclie der Immunitat, Heilung von Infectionskrankheiten. Munch, 
med. Woch., 1891; Infection, Immunisirung u. Heilung bei krup. Pneumonic. 
Zeit. f. Hyg.. xvii., 1894. 

Emmerich and Low: Bakteriolytische Enzyme als Ursache d. erworb. Imnumitat u. 
Heilung von Infectionskrankheiten. Zeit. f. Hyg., 31 Bd., 1899. 

Engelmann: Serumtherapie des Tetanus. Miinch. med. Woch., 1897 (Lit.). 

Ferran: L'inocul. preventive contre le cholera-morbus, Paris, 1892. 

Finger: Immunitat u. Phagocytose beim Rotz. Beitr. v. Ziegler, vi., 1889. 

Fliigge: Abschwachung virulenter Bakterieu u. erworb. Inuuuuitat. Zeitsehr. f. 
Hyg., iv. (Arbeiten von Smirnow, Sirotinin u. Bitter), 1888. 

Foa: Sur I'infection par le diplococcus lanceolatus. Arch. ital. de biol., xx., 1893. 

Foa u. Bonome: Ueber Schutzimpfungen. Zeitsehr. f. Hyg., v., 1889. 

Eraser: Immunization against Serpents' Yenom. Brit. Med. Journ., 1., 1896. 

Frisch: Die Behandlung der Wuthkrankheit, Wien, 1887. 

Galeotti: Immunit. u. Bakteriotherapie gegen Chorera. Cbl. f. allg. Patli.. vi., 1895 
(Lit.). ^ 

Gamaleia: Etude sur la vacinnation charbonneuse. Ann. de I'lnst. Past., 1888. 
Ganghofner: Die Serumbehandlung der Diphtlierie, Jena, 1897. 

Gay: \'accination and Serum Therapy against the Bac. of Dysentery, Univ. of Penn. 
Mrd. Bull., 1902. 

Glinther: Die Blutserumtlierapie. Deut. med. Wocli . 1893, Referat. 

Hess: Rauschbrand. Thiermed. Yortrage, 1 Bd., 4 H., Llalle, 1888; Die Schutzimp- 
fungen geffeu Rauschbrand im Kant. Bern in d. J. 1882-89, Bern, 1884, 1886 and 
1889. 

Hog-yes: Lyssa, Wien, 1897. 

Issaeff: Kiinstliche Immunitat gegen Cholera. Zeitsehr. f. Hyg., xvi., 1894. 

Kitt: Der Rauschbrand. Cbl. f^ Bakt.. i., 1887; GeHiigelcholera u. deren Schutzimp- 
fung. Deut. Zeit. f. Thiermed.. xiii. ; Cbl. f. Bakt., i. 1887. 

Kitasato: Heilversuche an tetanuskranken Tliieren. Zeitsehr. f. Llj'g., xii., 1892. 

Klemperer: Immunisirung u. Heilung bei Pneumokokkeninfection. Berl. klin. 
Woch., 1891. 

Knorr: Entstehung d. Tetanusantitoxins. Fortschr. d. jVIed., xv., 1897. 



THE ACQUIRING OF IMMUNITY. 



121 



Koch: Milzbrandimpfung, Berlin, 1SS2\ 31ittheil. a. d. K. Gesuudheitsamte, Berlin, 

1884; Xeue Tuberkulinpraparate. Deut. med. AVoch., 1897, No. 14. 
KoMer: Serumtherapie des Tetanus (Statistik). Miincli. med. Woch., 1898. 
Kolle: Active Immunisirung gegen Cholera. Cbl. f. Bakt., xix., 1896 (Lit.); Bakter- 

iologie der Beuleupest. Deut. med. Woch., 1*897 (Lit.). 
Kossel: Behandlung der Diphtheric mit Diphtherieheilserum. Zeit. f. Hjs:.. xvii., 

1894; Antitoxin wirkuug. Berl. klin. Woch., 1898. 
Landau: Diphtherieheilserum. Eulenburg's Encyklop. Jahrb., vi., 1896 (Lit.). 
Lofl9.er: Zur Immunitatsfrage. Mitth. a. d. K. Gesuudheitsamte, i. ; Immuuisirungs- 

Heilversuche gegenuber d. Infection mit Milzbrand-, Tetanus- u. Diphtherie- 

Bacillen. Cent. f. Bakt., ix., 1891. 
Loffler u. Abel: Specilische Eigenschaften d. Schiitzkorper. Cbl. f. Bakt., xix., 1896. 
Long-cope: A Study of the Bacteriolytic Serum-complements in Disease. Univ. of 

Penu. 3Ied. Bull., 1902. 
Lydtin u. Schottelius: Der Rotlilauf der SchTveine, Wiesbaden, 1885. 
Maiselis: Durch Ueberstehen v. Infectionskrankheiten erworb. Immun. Yirch. Arch., 

137 Bd., 1894. 

Marag-liano: La sieroterapia nella tubercolosi, Milano, 1897. 

Marx: Theorie der Schutzimpfuug gegen Tollwuth. Deut. med. Woch., 1900. 

Metschnikoff: Etudes sur I'immunite. Ann. de I'Inst. Past., 1890, 1891, 1894, and 

1895; Rech. sur Tinfluence de I'organisme sur les toxines. lb., 1897, 1898. 
Mosny: Vaccination et guerison de I'infection pueumonique. Arch, de med. exp., 

1898 (Lit.). 

Oppenheimer : Toxine u. Schutzstoffe. Biol. Cbl.. xix.. ls99 (Lit.). 
Pasteur: Sur la rage. Ann. de I'Inst. Past., i., 18.^7; Lettre a M. Duclaux. lb., ii., 
1888. 

Perroneito: Studien liber die Immunitiit gegen Milzbrand. Cbl. f. Bakt., v., 1889. 
Petruschky: Immunitiit des Frosches gegen Milzbrand. Beitr. v. Ziegler, iii., 1888; 

Wissensch. Grundlaoe d. Serumtherapie. Samml. klin. Yortr. . Xo. 212, Leipzig, 

1898. 

Pfeiffer u. Kolle: Schutzimpfung gegen Typhus. Deut. med. Woch., 1896. 
Raynaud: Role du sang dans la transmission de I'immunite vaccinale. Compt. Rend., 
t. 84, 1877. 

Rodet: L'attenuation des virus. Rev. de med., vii., 1887, and viii., 1888; Les inocu- 
lations vaccinales, L'immunite acquise, lb., viii., 1888, et ix., 1889. 

Rog-er: Schutzimpfung gegen Rinderpest. Zeit. f. Hyg., 35 Bd., 1900. 

Roux: Immunite contre le charbon symptomatique confere par des substances solu- 
bles. Ann. de I'Inst. Past., 1888; De I'immuuite. lb., 1891; Les serums antitox- 
ines. lb., 1894. 

Roux et Borrel: Tetanus cerebral et immunite. Ann. de I'Inst. Past., 1898. 

Roux et Chamberland : Immunite contre la septicemie confere par des substances 

solubles. Ann. de I'Inst. Past., 1887; Immunite contre le charbon. lb., 1888. 
Stephens and Meyers: Action of Cobra Poison on the Blood. Journ. of Path., v., 

1898. 

Stern: Ergebnisse auf d. Gebiete der Immunitatslehre. Cbl. f. allg. Path., 1894; 
Wirkung d. menschlichen Blutserums auf die exper. Tvphus-Infection. Zeit. f. 
Hyg., xvi., 1894, 

Steuer: Serumbehaudlung d. Tetanus. Cbl. f. d. Grenzgeb. d. ]\Ied., iii., 1900. 
TarufB.: Heilung des Tetanus traumaticus durch Antitoxin. Cbl. f. Bakt. xi., 1892. 
Tavel: Beitr. z. Blutserumtherapie d. Tetanus. Corrbl. f. Schweizer-Aerzte, 1894. 
TscMstowitsch.: L'immunisation contre le serum d'anguille. Ann. de I'Inst. Past., 
1899. 

Vaughan and Novy : The Cellular Toxins, 1902. 

Voges: Die Choleraimmunitiit. Cbl. f. Bakt., xix., 1896 (Lit.). 

Wasserman: Immunitiit. Eulenburg's Jahr., iv., 1894; Zeit. f. Hyg., xxii., 1896; 

Serumtherapie. Deut. med. Woch., 1897; Kiinstl. Immunitat. Berl. klin. Woch., 

1898; Seitenkettenimmunitiit. lb., 1898; IMeue Versuche auf dem Gebiete der 

Serumtherapie. Deut. med. Woch., 1900. 
"Weigert: Arbeiten zur Theorie der Antitoxinimmunitiit. Ergebn. d. alls:. Path., iv., 

1899. 

Welch :^The Huxley Lecture. Bull, of the Johns Hopkins Hosp., 1902. 
Yabe : Etude sur I'immunite de la tuberculose, Paris, 1900. 
Yersin: La peste bubonique. Ann. de I'Inst. Past., 1897. 
See also §§ 30 and 31. 



122 



HEMOLYSINS; IMMUNE-SERA. 



{Hcemolysins ; Immune-sera against Cells. ) 

Bordet: Les serums liemolytiques. Ann. de I'lust. Past., xiv., 1900. 

Bruere: On the H?emolytic Potency of Certain Sapotoxins Dissolved in Blood-Serum. 

Jour, of Med. Res., 1902. 
Bullocli: On the Nature of Haemolysis. Trans. Lon. Path. Soc, 1901. 
V. Dungern: Globulicide Wirkungen des thier. Organismus. Miincli. med. Woch., 

1899; Immunserum gegen Epithel. lb., 1899; Beitrage zur Immunitatslehre. 

lb., 1900. 

Ehrlich u. Morg-enrotli : Ueber Hamolysine. Berl. klin. Woch., 1900. 

Flexner: The Pathology of Lymphotoxic and Myelotoxic Intoxication. Univ. of 

Penn. Med. Bull., 1902. 
JFlexner and Noguchi: Snake-Yenom in Relation to Haemolysis, Bacteriolysis, and 

Toxicity. Univ. of Penn. Med. Bull., 1902. 
Halhan: Agglutinationsversuche mit Miitterlichem u. Kindlichem Blute. Wien. klin. 

Wochensch., 1900. 

Kyes: Ueber die Wirkungsweise des Cobragiftes. Berl. klin. Woch., 1902. 
Iiandsteiner : Spec, auf Blutkorperchen wirkende Sera. Cbl. f. Bakt., xxv., 1899. 
Xievin: The Influence of the Spleen on Natural or Acquired Hosmolytic Properties of 

Blood-Serum. Jour, of Med. Research, 1902. 
Metschnikoff : Sur les cj^totoxines. Ann. de ITnst. Past., 1900. 
Moxter: Immunserum gegen Spermatozoen. Deut. med. Woch., 1900. 
Noguclii : The Interaction of the Blood of Cold-blooded Animals, with Reference to 

Haemolysis, Agglutination, and Precipitation. Univ. of Penn. Med. Bull., 1902; 

A Study of Immunization, Haemolysins, Agglutinins, Precipitins, and Coagulins in 

Cold-blooded Animals. Ibid. ; The Anti-haemolytic Action of Blood-Sera, Milk, and 

Cholesterin upon Agaricin, Saponin, and Tetanolysin, etc. lb. 
Stewart: The Mode of Action of Various Laking Agents on the Blood -Corpuscles. 

Jour, of Med. Res., 1902. 
Sweet : A Study of a Haemolytic Complement found in the Serum of the Rabbit. Univ. 

of Penn. Med. Bull., 1902. 



CHAPTER IV. 



Disturbances in the Circulation of the Blood and of 

the Lymph. 

I. General Disturbances of the Circulation Dependent upon Changes 
in the Function of the Heart, Changes in the General Vascular 
Resistance and Changes in the flass of the Blood. 

§ 33. The mass of blood is kept constantly in motion by means of the 
rhythmical contractions of the auricles and ventricles of the heart. The 
blood, as it is driven into the elastic tube of the aorta toward the periph- 
ery of the body, meets a significant degree of resistance, which is caused 
by the friction in the innumerable divisions and subdivisions of the 
arterial system. This resistance occasions a relatively high pressure 
throughout the entire arterial system, which in the human femoral artery 
equals that of about 120 mm. of mercury. After passing through the 
capillaries the blood arrives in the veins with very little velocity, and 
stands in the veins under a very slight pressure, which varies according 
to the location of the vein, and is greatest where a high column of 
blood rests ui)on the lumen of the vein. In the great venous trunks in 
the neighborhood of the thorax the x^ressure is usually negative, espe- 
cially during inspiration, as the thorax during this stage of respiration 
aspirates the blood from the veins lying outside of the chest. Only dur- 
ing forced expiration does the j)ositive pressure in the veins rise some- 
what higher. 

Assuming the mass of the blood to be constant, the degree of pressure 
within the aorta, at any given moment, is dependent u^dou the work of the 
heart and the resistance in the arterial system. The latter in turn is 
dependent upon the variations in the total diameter of the combined 
cross-sections of the blood-vessels, due to the elasticity and contractility 
of the arteries. In the major circulation the arterial tone is very pro- 
nounced ; in the lesser circulation it is slight, the blood-pressure in the 
pulmonary artery being only from one-third to two-fifths that in the 
aorta. Both the heart and the arteries are under the influence of the 
nervous system, which regulates their activity. 

The activity of the heart consists in rhythmical contractions of its 
musculature ; and its normal efficiency presupposes that the heart-mus- 
cle, and also the cardiac ganglia, are sound. Every disease of the heart, 
therefore, in so far as it diminishes the contractile capacity of the heart- 
muscle and lessens the activity of the ganglion -cells, and in so far as a 
lessened functional activity of certain parts of the cardiac muscle is not 
compensated by an increased activity of other parts, will diminish the 
functional capacity of the heart. 

In many cases in which the functional capacity of the heart-muscle 
is impaired, certain anatomical changes, such as fatty degeneration and 
necrosis of its cells, can be demonstrated ; in other cases no anatomical 

123 



124 



DISTURBANCES OF THE CIRCULATION. 



changes can be made ont, especially in those cases in which the diminu- 
tion of working -capacity follows the exhaustion caused by excessive 
overexertion. This may occur when the heart is forced to work for 
some time only slightly above the normal, but under unfavorable condi- 
tions, as, for example, in cases of elevation of the body - temperature ; as 
well as in cases when for a short period it is overworked to an excessive 
degree. Under certain conditions disturbances of nutrition and intoxi- 
cations, such as occur in the infectious fevers, as well as a sudden 
diminution in blood-supply from the obstruction of a coronary artery, 
may cause an insufficiency of the heart within so short a time that the 
heart -muscle presents no recognizable anatomical lesion. The work of 
the heart may also be made difficult at times through the formation of 
adhesions between the epicardium and pericardium, and between the lat- 
ter and the contiguous pleura, in consequence of which the contractions 
of the heart are hindered. 

Through the collection of fluid in the pericardial sac in the course 
of certain diseases, further, through marked deformities of the thorax 
causing an abnormal smallness of the thoracic cavity, and through a high 
position of the diaphragm, the diastolic dilatation of the heart and the 
free afflux of blood from the veins may be hindered to such an extent 
that the ventricles receive too little blood. If, following pathological 
processes in the heart-valves, there result rents or distortions of the flaps 
or adhesions between them, or if in case of dilatations of the heart and 
the v alvular orifices the valve-flaps become relatively too short, there 
may arise those conditions of the auricular and ventricular orifices known 
as insufficiency and stenosis. The former condition is characterized by 
a failure of a valve to close completely during the diastole of the auricle 
or ventricle lyii^g behind the given valve ; the second condition, by th^ 
fact that during the contraction of the auricle or ventricle the valvular 
orifice does not suffice for the passage of the blood through the opening. 
The effect of a stenosis is that of opposing additional obstacles to the out- 
flow of the blood during systole. In aortic and pulmonary insufficiency 
the blood regurgitates, during the ventricular diastole, back from the 
great vessels into the ventricles ; in mitral and tricuspid insufficiency the 
systole of the ventricle causes a regurgitation into the corresponding; 
auricle. 

Finally, there are not infrequently formed in the heart masses of 
coagula, which under certain conditions — in case they lie near the orifices 
— may on the one hand interfere with the proper closing of the valves, 
or on the other cause a narrowing of the ostium. 

As the result of all the above-mentioned pathological conditions, the 
efficiency of the heart's function is impaired, so that in a given time 
too little blood passes into the arterial system, the aortic pressure conse- 
quently falls, and the velocity of the blood-current is diminished ; while 
in the venous system the blood collects more and more, and the venous 
pressure rises. There is consequently an inadequate filling of the arteries 
throughout the entire body, varying, indeed, according to the degree of 
contraction maintained in individual arterial systems, while both ^ eins 
and capillaries are, on the other hand, overfilled with blood. There 
develops, therefore, a condition of general venous hypersemia, which 
in some parts may become so marked that the tissue, because of the en- 
gorgement of the capillaries with venous blood, acquires a hlue-red, cya- 
notic appearance. When the difference in i)ressure between the arterial 
and venous systems becomes reduced to a certain minimum, the circula- 



IMPAIRMENT OF CARDIAC FUNCTION. 



125 



tioii comes to a standstill, while the right side of the heart becomes 
greatly distended with blood. 

Shonld the contractions of the heart from any cause become weak and 
imx^erfect, the pulse-wave also becomes small. If the rate of the heart- 
beat becomes diminished in frequency, the arterial system empties itself 
to a greater extent than normally during the imi^se between the systoles. 

If the impairment of cardiac efficiency involves the left heart essen- 
tially, as is the case, for instance, in valvular disease of the left side, the 
disturbance of circulation is manifest first in the systemic arteries, as 
well as in the pulmonary vessels. 

In stenosis of the aortic valves, the arteries, if the heart's action re- 
main unchanged, fill but slowly and incompletely (pulsus tardus). In 
aortic insufficiency a normal or even an increased amount of blood is 
thrown into the arteries during systole (pulsus celer), but a part of this 
flows back again during diastole. In both cases the left ventricle be- 
comes more and more distended, the emptying of the left auricle is hin- 
dered, its cavity also becomes dilated, and finally the blood is backed up 
in the pulmonary veins. Owing, however, to the low pressure in the 
pulmonary circulation, the blood is readily dammed back upon the right 
ventricle, and the blood stasis may finally extend beyond this into the 
right auricle and into the systemic veins. 

Valvular lesions at the mitral orifice produce similar effects ujion 
those portions of the circulatory a^Dparatus lying behind the left auricle, 
as in such cases there is produced also a condition of pulmonary stasis, 
with a rise of pressure in the jDulmonary arteries and veins ; while the 
left ventricle either receives too little blood (stenosis) or during its con- 
traction drives a portion back into the auricle (insufficiency). 

In valvular lesions of the orifices of the right heart the damming back 
of the blood is limited to the veins of the systemic circulation, while in 
the pulmonary circulation both pressure and velocity are diminished. 
Further, the pressure in the aorta also falls, since the left side of the 
heart receives too little blood. 

The damming back of the blood in the great systemic veins may 
manifest itself by venous pulsations in the neighborhood of the thorax, in- 
asmuch as retrograde waves of pressure proceeding from the heart may 
pass through the veins toward the capillaries, distending the veins to 
such an extent that the venous valves, particularly those of the jugular 
bulb, are rendered inadequate. The essential condition of the transmis- 
sion of the venous pulsation is the insufficiency of the venous valves. 
In the case of imperfect function of the valve in the jugular bulb, a 
slight pulsation may be observed even during normal action of the heart ; 
but when the veins are distended, and particularly in the case of tricus- 
pid insufficiency, the pulsation becomes much stronger and extends 
further toward the periphery. If the tricuspid is adequate the venous 
pulsation (presystolic) is only the expression of the rhythmical occur- 
rence of a hindrance to the outflow of blood from the veins (negative or 
normal venous pulse). In tricuspid insufficiency the contraction of the 
right ventricle forces blood back through the tricuspid opening into the 
right auricle and into the veins beyond, giving rise to a systolic venous 
pulsation (positive venous pulse). 

If in a heart affected with a valvular lesion the chambers lying be- 
hind the lesion become distended with blood, the muscular walls of these 
chambers, in case they are otherwise normal, may by an increased ac- 
tivity compensate for the valvular lesion within certain limits. In the 



126 



DISTURBANCES OF THE CIRCULATION. 



course of time tliere results au iucrease in the volume of the heart-mus- 
cle, a hypertrophy of the heart=muscle, which euables the heart to carry 
on its increased work for an indefinite period. Such compensation fre- 
quently becomes inadequate, with the result that the aortic pressure is 
permanently lowered, while the venous pressure, on the other hand, is 
abnormally high. There is, at the same time, the danger that the heart- 
muscle may in time become exhausted, or that a very slight illness may 
render the heart insufficient. Thus, for example, a prolonged quicken- 
ing of the heart's rate, by shortening the diastolic periods of rest, may 
cause cardiac exhaustion and insufficiency. Arrest of the heart's action 
finallj^ follows, with great accumulation of blood in the heart, since the 
heart is no longer able to drive onward the mass of blood entering it. 

Au increase of the heart's action — that is, an increase in the fre- 
quency of the heart's contractions, these at the same time remaining 
strong and complete — causes an increase in arterial pressure and an in- 
creased velocity of the blood-current. When increased demands are fre- 
quently made upon the left side of the heart — as frequently hapi^ens in 
heavy bodily labor, conditions of luxurious living, abnormal irritability 
of the cardiac nerves, etc. — the left ventricle may become hypertrophic 
and act permanently with greater force. Inasmuch as the quickening of 
the blood- stream causes the right heart to receive a greater amount of 
blood during diastole, a hypertrophy of the right ventricle is usually 
found in connection with the hypertrophy of the left ventricle. 

Lessening of the mass of blood or general anaemia from the loss of 
blood leads temporarily to a fall of pressure in the aorta ; but if the loss 
of blood was not excessive, the blood-pressure rises again, as the vessels 
adapt themselves to the changed conditions, and, as the result of the 
stimulation of the vasomotor centre through local anaemia, show a 
greater degree of contraction. Under normal conditions the mass of blood 
is quickly increased through the absorption of fluids, and later by a re- 
generation of the blood. Similarh^ in anhydr^emia — i.e., a diminution 
of the water of the blood — the arterial pressure is lowered and the blood- 
current slowed. After severe haemorrhages the arterial pressure is low- 
ered for a greater leogth of time, the circulation is slowed, and the pulse, 
because of the lessened stimulation of the vagus-centre (Cohnheim), is 
frequent and small. 

In the case of lasting diminution of the blood-mass — i.e., the condi- 
tion known as chronic anaemia, which occurs under varying conditions 
— the vascular system is imperfectly^ filled, the blood-pressure lowered, 
and the blood -current slowed. Both heart and blood-vessels adapt them- 
selves to the new conditions and become diminished in volume. In the 
case of a marked deficiency of haemoglobin, degenerations of the heart- 
muscle, particularly fatty degeneration, frequently occur. 

Increase in the mass of the blood, through the injection of blood or 
salt-solution into the blood-vessels, is followed in animals by only a tem- 
porary increase in pressure and in the velocity of the blood- current. A 
return to the normal is brought about, partly by the dilatation of a part 
of the vascular system, particularly in the abdomen, and partly through 
the elimination of the sui*plus from the vessels. If the mass of blood, as 
the result of some especial predisposition or of high living, comes to 
stand in an abnormally high porportion to the body- weight, if there 
exists a permanent plethora, the pressure in the aorta becomes perma- 
nently raised, the work of the heart is j)ermanently increased, and there 
develops a corresponding Imjyertropliy of the heart. 



CHANGES IN BLOOD PRESSURE. 



i2r 



§ 34. Increase of the general vascular resistance may occur in 
either the greater or the lesser circulation, and results in an increased 
pressure behind the point of increased resistance, and a diminished press- 
ure beyond it. 

In the systemic circulation the hindrance may lie either in the maiu 
vessel, the aorta, or in the arterial branches, whose degree of contraction 
maintains and governs the normal pressure in the aorta. Vascular con- 
traction involving a great number of arteries and their branches, and 
sufficiently well marked to increase the blood-pressure, is generally a 
temporary phenomenon, passing off with the relaxation of the arterial 
tension, is^evertheless, a permanent increase in the aortic pressure with 
consequent hypertrophy of the left ventricle does occur ; and this cannot 
be explained otherwise than as the result of the contraction of the lumen 
of the smaller arteries. Transitory arterial contraction and increase of 
pressure occur particularly through an increase of the amount of car- 
bonic acid contained in the blood. A permanent increase of aortic 
pressure is, on the other hand, a result of chronic diseases of the kidney, 
in which the secreting parenchyma is destroyed. Inasmuch as the por- 
tion of the vascular system which is thus cut off is much too small to 
cause such an increase of pressure throughout the whole aortic system, 
since the vessels leading to other organs might become correspondingly 
dilated, it must be assumed that in the case of contracted kidney some 
other hindrance to the circulation occurs throughout more extensive 
vascular areas. This hindrance would most naturally be sought in the 
apparatus which normally serves to keep the aortic pressure at its x)roper 
height, namely, in the smaller arteries of the hodj. Whether the condi- 
tion is caused by nervous stimuli arising in the kidney, or by the action 
of retained urinary substances upon the vasomotor centres or directly 
upon the v essel-walls, or whether the heart is excited by nervous stimuli 
to increased action, we are not at present able to say. 

Increase of resistance in the aorta may result from stenosis of this 
vessel, as occurs in rare cases at the isthmus, or from congenital narrow- 
ings of the whole aorta, large aortic thrombi, or from extensive disease of 
the vessel-wall, in consequence of which the intima is rough and nodu- 
lar, the entire vessel rigid, inelastic, and unjdelding ; or, finally, from a 
general dilatation of the vessel, whereby eddies are formed in the blood- 
stream. 

Lowering of the total resistance in the systemic circulation is pos- 
sible through the relaxation of the tone of a large part of the arteries, 
and this event may happen when the vasomotor centre is parah^zed, or 
when the cervical cord is divided or partly destroyed through any other 
process. Since the blood, in this case, flows abnormally quickly from 
the arteries into the veins, the difference in blood-pressure between the 
arteries and veins is lessened, the current becomes slower, the heart re- 
ceives too little blood during diastole, and, finally, the circulation may 
come to a standstill. 

Increase of the resistance in the pulmonary circulation occurs most 
frequently as the result of disease of the lungs and XDleura. Adhesions 
of the pleura, as well as spinal curvatures, which hinder the expansion 
of the lungs and their change of volume during inspiration, thereby de- 
priving the circulation of an efficient aid, may cause such increase of 
pulmonary resistance. Of great influence, moreover, are such affections 
of the lung as idiopathic emphysema, retractions and indurations of the 
lung, and destruction of lung -tissue — all of which lead to the oblitera- 



128 



DISTURBANCES OF THE CIRCULATION. 



tion of a portion of the pulmonary capillaries ; further, compression of 
the lung through pleural exudate; and, finally, compression of the pul- 
monary arteries by aortic aneurism or by tumors. 

If the hindrance is only slight, the blood may make for itself a new 
passage to the left heart without any increase of pressure ; the rate of the 
current in the blood-vessels which are unobstructed alone being increased. 
Gj'eater obstacles cause an increase of pressure in the pulmonary artery 
and the right heart, and if the condition persists for some time the right 
ventricle through increased exertion may become hypertrophic. This 
can occur, however, only when the heart-muscle is adequately nourished 
and when the mass of the blood is not diminished to correspond to the 
diminution of the area of the pulmonary vessels. If the right heart is 
not able to overcome the obstacles in the pulmonary circulation, the 
blood is dammed back upon the right heart, and eventually upon the 
systemic veins. 

An increase of the pressure in the right side of the thorax hinders the en- 
trance of the venous blood into the right heart, and causes an accumula- 
tion of blood in the systemic veins. A sudden increase of pressure may 
cause a retrograde flow of blood into the neighboring veins. 

According to the investigations of Bomherg, Pdssler, Bruhns, and Midler, pneumo- 
cocci, diphtheria-bacilli, and the Bacillus pyocyaneus injure the circulatory apparatus 
of the rabbit, in that they 'cause paralysis of the vasomotor centres in the medulla. 
This paralysis leads to a diminution of the arterial blood-pressure and to a change in 
the distribution of the blood. The splanchnic vessels become overfilled, the vessels of 
the brain, skin, and the muscles become empty. The heart is not concerned in this 
disturbance of the circulation. In general, it is affected secondarily as a result of the 
deficient flow of blood due to the vasomotor paralysis. A central paralysis oj^ the mso- 
motors is also responsible for the circulatory disturbances occurring in the acute infec- 
tions ; and is the chief cause of the failure of the circulation. 

The observation that hypertrophy of the heart follows different diseases of the 
kidneys has been interpreted in various ways. Some writers seek the cause in an in- 
crease of the volume of the blood {Trauhe, Bamberger), others {Senator, Ewald) believe 
it to be due to the changed character of the blood, while others {Gvll and Sutton) 
ascribe it to a widespread- change in the walls of the small arteries. Bidil holds that it 
is due to the over-nourishment of the heart. According to the investigations made up 
to the present time, there can be no doubt that the hypertrophy of the heart in diseases 
of the kidney is dependent upon an increase of the aortic pressure. This increase is 
best explained by an increase of the resistance in the small arteries of the entire body, 
due to the contraction of the ^mall arteries. This contraction must be brought about 
either through the direct action of the urinary substances contained in the blood or by 
some reflex stimulus from the kidneys, or finally by some influence exerted upon the 
vasomotor centre. It is possible that the heart also may be excited to increased 
activity. 

Literature. 

{Disturhances of the Circulation.) 

Bamberger: Ueber Morbus Brightii. Samml. klin. Vortr., No. 173, 1879. 
V. Basch: Allgem. Physiologic u. Pathologic des Kreislaufs, Wien, 1892. 
Cohnheim: Vorlesungen liber allgem. Pathologic, Berlin, 1882. 
Gull and Sutton: Med.-chir. Transact., Iv., 1852. 

Janowski: Diagnost. Bedeutung der Pulsuntersuchung. Klin. Vortr., Nos. 192. 
198, Leipzig, 1897. 

Jiirgensen: Ei'krankung d. Kreislauforgane, Insufficienz des Herzens, Wien, 1899. 
Krehl : Pathologische Physiologic, Leipzig, 1898. 

Lowit: Ueber die Entstehung des Lungenodems. Beitr. v. Ziegler, xiv., 1893. 
Lukjanow: Allgemeine Pathologic des Gcfasssystems, Leipzig, 1894. 
Mackenzie: The Venous and Liver Pulses. Journ. of Path., ii., 1893. 
Romberg, Passler, Bruhns u. Miiller: Kreislaufstorung bei acuten Infections- 
krankheiten. Deut. Arch. f. klin. Med., 64 Bd., 1899. 



LOCAL HYPEREMIA; LOCAL ANEMIA. 



129 



Rosenbach: Herzkrankheiten. Eulenburg's Realencyklop. ; Einfluss der Raumbe- 

sclirankung in der Pleiirahohle auf den Kreislauf. Vircb. Arcb., 105 Bd., 1886. 
Thoma: Patbolog. Anatomie, i., Stuttgart, 1894. 
Traube; Ges. AbbandUuigen, Berbn, 1874-78. 

II. Local liyperasmia and Local Anaemia. 

§ 35. To the blood is assigned the function of snpphing all the or- 
gans aiid tissues of the body with nourishment. The cells and cellular 
structures of which the various tissues are comijosed are able to maintain 
their existence without the advent of fresh nutritive material only for a 
short time; and for this reason the majority of the tissues are supplied 
with blood-vessels, and those not possessing vessels of their own are 
placed in the most intimate connection with vascular structures. 

The demands of the different tissues for blood are not always the 
same, and there is consequently in the various tissues a corresponding 
increase or decrease in the afflux of blood and in the amount of blood 
contained within an organ or tissue at any given moment. An organ 
rich in blood is designated as hyper^mic ; one poor in blood as ansemic. 

Tlie regulation of the amount of blood which an organ receives under 
physiological conditions is brought about by a change of the resistance 
in the afferent arteries ; and this change is effected entirely through a 
variation in the calibre of the arteries. Since the total mass of the 
blood in the body is not sufficient to fill all the vessels at the same time, 
an extra supply of blood to one organ is possible only by sui)plying a 
less amount of blood to other parts. The change in the calibre of an 
artery is determined, aside from the blood-pressure, by the elasticity of 
the artery-wall and the degree of contraction of its smooth muscle-fibres. 
These fibres are the regulating element; their activity is dependent 
partly upon influences affecting them directly, and partly upon ner- 
vous influences from the intravascular plexuses and from the vasomotor 
centres in the medulla oblongata and in the spinal cord, some of these 
stimulating, others inhibiting the muscular action. 

When the departures from the average blood-supply of any part of 
the body overstep the i3hysiological limits, or if such variations arise 
without physiological causes, or are unduly prolonged, the condition is 
spoken of as pathological hypersemia and pathological anaemia. These 
conditions are in part brought about by the same regulating mechanism 
which governs the normal blood-supply of an organ. 

g 36. Hypersemia of an organ is caused under pathological con= 
ditions either by an increase in the arterial supply or through an ob- 
struction and damming-back of the venous outflow ; and there are dis- 
tinguished, accordingly, two forms, an active or congestive {arterial) 
hijperwmia and a passive or stagnation (venous) liypercemia. Active hy= 
peraemia arises through an increase of the afflux of blood {congestion), and 
may be either idiopathic or collateral. The first of these plays the more 
important role. It depends upon a relaxation of the muscular tunics of 
the artery, which may be brought about either by paralysis of the vaso- 
constrictors (neuroparalytic congestion), or through a stimulation of the vaso- 
dilators (neurotic congestion), or through direct iveakening Siud paralysis of 
the muscles (as, for instance, by heat, bruising, action of atropine, brief 
interruptions of the blood- current), or, finally, through a diminution of 
the external pressure exerted upon the vessels. Collateral hypercemia is 
merely the result of a diminished flow of blood to other parts. It oc- 
9 



130 



DISTURBANCES OF THE CIRCULATION. 



curs first in the immediate neigliborhood of the parts whose blood- 
supply is lessened ; later, the blood may be driven also to such other 
more distant organs as may require it. 

Active hypersemia is characterized by a more or less marhed redness and 
swelling of the part, which are very striking in tissues rich in blood-ves- 
sels. The blood flows through the widened channels with increased 
velocity, and lends to the tissue the color of arterial blood. Superficial 
tissues which are exposed to cooliog become as a result of the increased 
blood -supply warmer than the neighboring tissues which are less richly 
supplied. 

Passive Hypersemia arises through the retardation or obstruction of 
the flow of blood f rom the veins. A general xxtssive congestion of the systemic 
veins occurs in those cases in which, through weakness of the heart's ac- 
tion, valvular insufficiency or stenosis, or obstructions to the pulmonary 
circulation, the emptying of the large veins into the right heart is hin- 
dered. In the pulmonary circulation stagnation of the blood-stream 
may be brought about by any cause hindering the outflow of blood from 
the lungs, particularly valvular lesions of the left heart, weakness of the 
left side of the heart, and, more rarely, obstructions in the systemic 
arteries, ^^'ot infrequently such a stasis of the ]3ulmonary circulation 
may reach such a degree that the blood is dammed back into the right 
heart, and into the veins of the systemic circulation (see §§ 33 and 34). 

Local passive congestion may arise directly from the fact that the 
progress of blood through the veins is not adequately supported by the 
activity of the muscles and the asi)iration of the blood from the veins dur- 
ing the inspiratory enlargement of the thorax. The absence of the first 
factor is most apparent in the case of the branches of the inferior vena 
cava I as, for example, in individuals who pass a large part of their time 
sitting or standing without acti^ e bodily exercise, so that the emptying 
of the deep-seated venous branches into the vena cava is dependent al- 
most whoUj^ upon the activity of the vein -walls, which by virtue of their 
elasticity and contractility work against the pressure of the column of 
blood resting upon them. The absence of the inspiratory aspiration of 
the venous blood may, on the other hand, make itself felt in disturbance 
of inspiration through inflammation or other disease-processes of the 
lungs or pleura. 

A further cause of local passive hj^persemia consists in the narrowing 
or closing of individual veins, as in the case of compression, ligation, 
formation of thrombi (§ 38), and the invasion of the veins new- 
growths. For exami)le, the pregnant uterus or a pelvic tumor may com- 
press the pelvic veins, a thrombus may obstruct the cerebral sinuses or 
the femoral or portal veins, or a sarcoma of the pelvis may grow into 
the large pelvic veins. 

When, through the above-mentioned processes or through ligation, 
single veins become occluded, the effect of the occlusion is often very 
insignificant, inasmuch as the veins concerned may possess free commu- 
nication with other veins, so that but slight obstruction is offered to the 
outflow of the blood. If, on the other hand, the occluded vein possesses 
no collateral communications, or very small ones which are inadequate 
for the passage of the blood — as, for instance, is the case with the main 
divisions of the portal vein, the sinus of the dura mater, the femoral and 
the renal veins — there results a more or less marked passive congestion 
in the area supplying the given vein. 

The effect of an obstacle to the outflow of blood shows itself first in. 



ACTIVE AND PASSIVE HYPEREMIA; HYPOSTASIS. 131 

that portion of the vein lying between the obstruction and the periph- 
ery, the blood -current becoming slowed or checked entirely, while at the 
same time there follows a progressive filling and dilatation of the veins 
through the continued afflux of blood from the capillaries. If through 
the counteractive effect of the Increasing tension of the elastic and con- 
tractile vein-walls the obstacle is overcome, the circulation is main- 
tained, and the blood flows toward the heart through the channels which 
it still finds open, l^ot infrequently the small veins thus called upon to 
perform this increased labor become gradually much dilated, and are 
converted into larger veins. When the obstacle cannot be overcome and 
communicating vessels capable of dilatation are not present, the circula- 
tion comes to a standstill, and a condition of stasis (§ 41) or thrombosis 
(§ 38) is produced in the obstructed vessel and its tributaries. 

If the congestion within a venous area extends to the capillaries, so 
that they become overfilled with blood, the affected tissue becomes blue- 
red or cyanotic, exhibiting at the same time a certain degree of swelling. 

Both active and passive hyiDersemia, observed during life, may, after 
death, show a very different appearance, and not infrequently disappear 
entirely. This is especially the case in the active hyperjemias of the 
skin, in part also in those of the mucous membranes. This is dependent 
upon the fact that the tissues, put upon the stretch by the dilatation of 
the capillaries, contract upon the latter, after the stoppage of the cir- 
culation, and by their counter-pressure drive the blood from the capil- 
laries into the veins. In this way a tissue which was red during life 
may become pale after death. On the other hand, tissues which during 
life were pale or at least showed no especial redness, may after death 
take on a blue-red color. This takes place particularly upon the sides 
and back of the trunk (in those parts not pressed upon by the body- 
weight), on the neck, and the j)osterior aspects of the extremities of 
cadavers lying upon their backs ; and is to be explained by the fact that 
after death the blood sinks to the most dependent parts of the body, and 
fills not only the veins, but finally also the capillaries. This phenome- 
non is known as post=mortern hypostasis, and the areas of discoloration 
as " death=spots " or livores. They appear within about three hours 
after death, and are the more pronounced the greater the amount of 
blood contained in the skin and subcutaneous tissues at the time of death. 

In the internal organs post-mortem hypostasis is particularly notice- 
able in the pia mater, the dependent veins being usually more markedly 
distended with blood than those situated higher. In the lungs the set- 
tling of the blood causes an engorgement not only of the veins, but also 
of the capillaries. 

If the general circulation during life, as a result of cardiac insuffi- 
ciency, is imperfect, and there results a general passive congestion, the 
blood may also collect in the dependent portions of the body, partly be- 
cause it is not driven out of them, and partly because it sinks into these 
parts from those situated on a higher level. This phenomenon is also 
known as hypostasis, and occurs particularly in the lungs (hypostatic 
congestion). 

For the observation of the circulation and its disturbances during life the tongue 
or the web of the curarized frog, properly spread upon a glass plate, may be used 
{Gohnheim, Virch. Arch., Bd. 40). This may be done in a very simple manner by draw- 
ing the frog's tongue over a cork ring, which is cemented to a glass plate, and fasten- 
ing it to the sides of the ring with pins. The pulsating arterial current and the con- 
tinuous venous stream possess a cl ' r zone of blood plasma, iu both the normal and 



132 



DISTURBANCES OF THE CIRCULATION. 



the quickened circulation. If, through tlie ligation of the efferent veins of the tongue, 
passive congestion is produced and the current slowed, the plasma-zone in the veins is 
lost, and both veins and capillaries become greatly distended with accumulated red 
cells. After a certain time the tongue swells as the result of an intiltration with trans- 
uded fluid. 

According to the investigations of xoii Landerer ("Die Gewebsspannung," Leipzig, 
1884), the w^all of a capillary vessel embedded in tissue supports only from one-third 
to one-half of the blood-pressure. The remaining portion is borne hy the tissues, which 
afford an elastic resistance, and thereby maintain the tension which is necessary to keep 
the blood in motion. In both active and passive hj'perjiemia both the tissues-pressure 
and the tissue-tension are increased ; in ansemia they are diminished. 

§ 37. Local anaemia or ischsemia, the lack of proper blood-supply 
to a tissue, is always the result of a diminution in the afflux of blood. 
If the total mass of the blood is normal, the cause of the anoemia is 
purely local ; if there is a general poverty of blood, the local ansemia, in 
part at least, is secondary. 

The pathological diminution in the blood=supply to an organ is at 
times mereh' the result of an abnormal increase of the arterial resistance, 
due to the contraction of the muscular coats. In other c^ses 2^((thological 
obstructions — such as compression of the arteries, narrowing of the 
arterial lumen through pathological changes in the vessel-walls, deposits 
on the inner surfaces of the arteries, occlusion of the vessels by emboli 
(compare § 20), etc. — may act as hindrances to the blood-stream. 

The immediate result of the narrowing of an artery is always a slow- 
ing and diminution of the blood-stream beyond the point of constriction. 
Comjylete occlusion of an arterj' brings the circulation beyond the obstruc- 
tion to an immediate standstill. If back of the point of constriction or 
occlusion the artery is provided with large arterial communicating 
branches — the so-called arterial collaterals — the disturbance of the circu- 
lation may be compensated hy an increased afflux of blood through the 
collateral arteries ; and this compensation is the more complete the larger 
and the more distensible are the collaterals. If the narrowed or occluded 
artery possesses no collateral branches in its area of distribution — if it is 
a so-called terminal artery — the slowing or cessation of the circulation be- 
yond the point of obstruction or occlusion cannot immediately be done 
away with, and the affected vascular area becomes partly or wholly emp- 
tied of blood, in that, through the contraction of the arteries and the 
pressure of the tissue on the capillaries and veins, the blood is almost 
wholly driven out of the area supplied by the obstructed artery. Fre- 
quently there occurs after a time an afflux of blood from the neighboring 
capillaries. 

When the current and the pressure beyond a constricted ijoint ha\ e 
sunk to a certain minimum, the driving force gradually becomes unable 
to propel the mass of blood. The red corpuscles, in particular, cease to 
move, and collect in the veins and capillaries, so that the area supplied 
by the aHery in question becomes again filed icith blood ; only not with cir- 
culating, but with stagnant blood. The same thing occurs tchen, after com- 
plete occlusion of a terminal artery, the blood slowly and under low press- 
ure enters the vessels of the affected area from small arteries incapable 
of adequate enlargement, or merely through anastomosing capillaries. 
Finally, an accumulation of blood within the anaemic area may also oc- 
cur by a reflux from the veins. This takes place when the intravascu- 
lar pressure within this area has sunk to nothing in the arteries and 
capillaries, while in the veins a positive pressure exists. A condition of 
passive congestion in the veins favors such a reflux. 



THE SEQUEL.^ OF ISCHEMIA. 



133 



A further cause of antemia of one organ may be found in the abnor- 
mal congestion of other organs, as in that case the total mass of the 
blood is not sufficient to suiDply adequately the remaining organs. Such 
an anaemia is designated collateral ancemla. 

All anwrnic tissues are characterized by At the same time 

they are tiabbj', not turgescent, and show their individual color more 
distinctly. 

The significance of ischsemia lies especially in the fact that, on ac- 
count of the need of the tissues for a continuous supply of oxygen and 
food-material, the persistence for a certain length of time of the condi- 
tion of imperfect blood-supply brings about tissue-degenerations (compare 
§ 1). Total arrest of the blood- su^Dply leads in a short time to the death 
of the tissue involved. If the blood comes to flow anew into the degen- 
erating and dying tissues in the area of distribution of an obstructed ves- 
sel, and there stagnates, an extravasation of blood into the tissue may 
take place, leading to the formation of a licemorrliagic infarct (compare 

The rapidity and completeness of tlie derelopmeiit of a collateral circulation after the 
occlusion of an artery depends upon the size and distensibility of tliose vessels which 
are in communication with those of the antemic area. If these are numerous and dis- 
tensible, the antemic area is soon again supplied with an approximately normal volume 
of blood. If this is not the case the disturbance of the circulation is more slowly com- 
pensated; and the stasis and increased pressure are found to extend farther back from 
the point of obstruction toward the heart, so tliat a collateral hypersemia occurs in ves- 
sels situated farther back toward the heart. In the further course of the process of 
re-establishing the circulation the resulting increase of volume and velocity remains 
coutined to such vessels as communicate with the area of the obstructed artery, that is, 
confined to the capillary and arterial anastomoses, where the increase of volimie and 
velocity become permanent. This leads furtlier to a lasting dilatation of the vessels 
concerned, and at the same time to an increase in the vessel-walls, not only in thickness, 
but also in length, as is evident from the increased tortuosity of the vessels. Accord- 
ing to Xotlinagel, the phenomenon of the increase in thickness of the w^alls of the anas- 
tomosing arteries m?Lj be demonstrated in the case of rabbits in about six days after 
the ligation of an artery ; and after the ligation of large vessels in their continuity, the 
small arteries which carr}" on the collateral circulation become changed in the course 
of a few weeks, into quite capacious, thick-walled arteries. 

Literature. 

{Local Disturbances of Circulation.) 

Baldwin: Multiple Anti^mic Infarction of the Liver. Joiu". of Med. Research, 1902 
(Lit.). 

Bier: Entstehung d. Collateralkreislaufs. Yircli. Arch., 147, 153 Bd.. 1897, 1898 (Lit.). 
Cavazzani: Sur ia genese de la circulation collaterale. Arch. ital. de biol., xvi., 1892. 
Cohn: Klinik der embolischen Gefiisskrankheiten. Berlin. 1860. 
Cohnheim: Tories, liber allgemeine Pathologic, Berlin, 1882. 
Hektoen: Embolism of the Coronary Arteries. Med. Xews, 1892. 

Krauss: Der Yerschluss der Vena Cava sup. u. d. Yeua Cava inf. Inaug.-Diss., Tu- 
bingen 1894 (Lit.). 

Lowit: Riicklautige Blutstromuug. Centralbl. f. a!lg. Path., viii., 1897. 
Lukjanow: AUgemeiue Pathologic des Gefasssvstems, Leipzig, 1894. 
Marchand: Gehirnembolie. Berl. klin. Wocheuschr., 1894. 

Mdgling: Zur Kenntn. des hauKu-rhaoischen Infarktes. Beitr. v. Zieeler, i., 1886. 
Nothnagel: Die Entstehung des Collateralkreislaufs. Zeitschr. f. klin. Med., xv., 
1888. 

V. Recklinghausen: Pathologic des Kreislaufs u. der Ernahruns:, Stuttgart, 1883. 
Reimar: Embolic der Art. centralis Retime. Arch. f. Aui^euheilk., o8 Bd., 1899. 
Saveliew: Gehirnarterienembolie. Virch. Arch., 135 Bd.T 1894. 
Talma: Leber collaterale Circulation. Pfliiger's Arch., 23 Bd., 1880 
Thoma: Patliologische Anatomic, i., Stuttgart, 1894. 

Virchow: Oertliche Storungen des Kreislaufs. Handb. d. spec. Path., i., Erlangen, 



134 



DISTURBANCES OF THE CIRCULATION. 



III. Coagulation, Thrombosis, and Stasis. 

§ 38. Upon the death of the individual the blood contained in the heart 
and great vessels sooner or hiter coagulates in part, and there arise those 
formations which are known as post=mortem clots. If the clotting oc- 
curs at a time when the red blood -cells are still evenly distributed in the 
blood, the whole mass of the blood becomes coagulated, forming soft, 
dark-red masses of coagulum which are known as cruor. If before the 
clotting there occurs, through the sinking of the red cells, a separation 
of the blood into two laj^ers — a substratum rich in red blood-corpuscles, 
and an upper fluid layer containing none and consisting only of the 
plasma — then, if the latter coagulate, there will be formed soft, gelat- 
inous, light-yellow, elastic lumps and stringy masses having a smooth 
surface and not adherent to the vessel-wall, which are known as lardace- 




FiG. 12.— Coagulated blood in a fresb hasmorrhagic infarct of the lung. (Miiller's fluid ; haematoxylin 
and eosin.) a. Alveolar septa without nuclei, containing capillaries tilled with dark bluish-violet, homo- 
geneous thrombus-masses ; i), septa containing nuclei ; c, vein filled with red thrombus ; d, di, alveoli 
filled with firm blood-clots ; e, alveoli filled with serous fluid, fibrin, and leucocytes. X 90. 

ous clots or fibrinous deposits. Through the inclusion of red cells in 
these formations, they may present in parts a red or reddish-black color ; 
if large numbers of leucocytes are present, they may have a whitish 
color. 

When blood is drawn from an artery or vein and received into a vessel, 
coagulation will occur within a, shoi t time, as the result of the adhesion 
of the fluid to the sides of the receptacle. The entire blood-mass be- 
comes changed into a soft coherent mass. When freshly draAvn blood is 
beaten with a solid body, the surface of the latter becomes covered in a 
very short time with felt-like fibrin. If tvithin the body large quantities 
of blood pass out into the tissues — as, for examj)le, into the pericardium or 
into the lungs — coagulation may occur here likewise, and the extravasated 
blood may in this way acquire a firm consistency. 

Under certain conditions there may be formed within the heart or 
blood-vessels during life, firm deposits, which in part are similar to cruor, 
and in part to the fibrin -masses formed by whipping the blood. These 
formations are known as thrombi, and the process which leads to their 
formation as thrombosis. According to their color they may be distin- 



COAGULATION OF THE BLOOD. 



135 



guislied as red, colorless or white (that is, yellow or grayish- white), and 
mixed thrombi. 

The coagulation of the blood is a peculiar process, difficult of exact 
interpretatiou. Histologically, it is characterized, both in extravascular 
clotting (Fig. 12, d, dj and in intravascular as well (Fig. 13), by the 
formation of little rods and threads between the red cells, at one time ar- 
ranged in a meshwork, at other times in stellate or fascicular groups 
around centres. These little rods and fibres are known as fibrin ; and 
are in part smooth and shining, in part covered by little granules, or 
partly interruiDted by granules, or are composed entirely of such collected 
together. Besides the threads there occur also free granules, granular 
masses, and Nood-jMes of varying size and form; and not infrequently 
such formations lie in the centre of the fibrin-stars. At times the stellate 
and fascicular forms of fibrin are found arranged about leucocj'tes or at- 
tached to endothelial cells of the iutima of the vessel. 

1)1 the red Mood-cells there occur here and there degenerative appear- 
ances, in the form of plasmolysis, plasmorrhexis, and x)lasmoschisis. In 
plasmolysis or erifthrociftolysis there occurs a passage of soluble substances 
from the red cells into the blood plasma, so that the red cells become 
smaller, and the so-called microcytes and red blood-cell shadows" are 
produced. At the same time individual cells may become swollen. 

In plasmorrhexis or erythrocijtorrhcxis and in plasmoschisis or erythro- 
cytoschisis, bright, shining globules arise from the red cells, or the latter 
become covered with little prickle-like projections, or come to resemble 
mulberries, or send out x3rotox3lasmic x)rocesses. Through the snaring- 
off of these prominences round, disc-like, angular, or thread-like bodies 
are formed, which are partly homogeneous and partly finely granular, 
and not infrequently enclose larger shining bodies. Finally, the red cells 
may break up into disc-like or globular pieces, and finally into granules. 
The formations known as hlood-plates are nothing more than peculiarly 
formed products of p>lasmorrhexis and 2:)l(ismoschisis of the red cells ; and it is 
possible to distinguish among them those which are colorless, those con- 
taining haemoglobin, and homogeneous and granular forms. 

In fresh coagula, changes cannot usually be demonstrated in the col- 
orless corpuscles of the blood ; but in the later course of the i)rocess degen- 
erative appearances are found in these also. 

Between the destruction of the red blood-cells and the coagulation of the 
blood, both extra- and intravascular, there exist undoubtedly close relations^- 
that is, coagulation is set into action through the occurrence of changes 
in the red cells as above described. According to our present knowledge, 
it must be assumed that many red cells, probably the oldest ones, very 
easily suffer such changes, so that, for example, adherence to a diseased 
portion of the vessel -wall, which is prevented by the normal condition of 
the intima, is sufficient to cause a disintegration of certain red cells, with 
formation of blood-plates, and later coagulation and thrombus-forma- 
tion. The origin of coagulation has also been regarded as due to i^las- 
molysis and plasmorrhexis of the leucocytes ; further, similar degenera- 
tions of the endothelium may also induce coagulation. The possibility 
that the endothelial cells play a certain part in the origin of coagulation 
cannot be excluded, but it must be emphasized that the degenerative 
changes ordinarily preceding coagulation cannot be demonstrated in these 
cells. The facts brought forth, particularly by Hauser and Zenker, that 
the fibrin-threads not infrequently are attached to endothelial cells, or 
leucocytes, or to the remains of such cells, do not prove that these are 



136 



DISTURBANCES OF THE CIRCULATION. 



" 5 




Fig. 13.— Bundles and star-shaped clusters of fibrin 
threads within a blood-vessel. (Fibrin staui.) Prepara- 
tion taken from an inflamed tracheal mucous membrane. 
X 500. 



the exciters of coagulation, or that they offer material for the formation 
of tibrin ; inasmuch as the deposit of the fibrin ux)on these cells may 

be due to purely mechanical 
causes. 

The chemical processes 

concerned in coagulation can- 
not at present be explained. 
It is assumed that for its oc- 
currence the presence of a 
fihrinogcnic substance, a fer- 
ment (tlu'ombin ), and certain 
salts, ])'<ivticii\-dvly calcium salts, 
is necessai'3' ; and that the 
fibrinogenic substance is an 
albuminoid body belonging to 
the globulins, which is present 
in the blood-plasma, while 
the ferment is produced b^' 
the cells. According to A. 
Schmidt, thrombin is derived 
from a parent-substance, pro- 
thrombin. By means of the 
thrombin there is formed, in au as yet unknown manner, from the globu- 
lins iDre-existing in the alkaline solution, a greatly swollen albuminoid 
body, which is precipitated by the calcium salts contained in the i^lasma. 
In the process of coagulation we must, therefore, recognize two stages, 
namely, the stage of the production of the fibrin -ferment, and the stage 
of the action of the ferment or coagulation proper. 

According to Pekelharing, on the other hand, thrombin is a calcium 
compound of prothrombin, which 
arises from the cellular elements 
of the blood; and coagulation 
. consists essentially in the fact 
that thrombin carries calcium 
over to the fibrinogen, wherebj' 
the insoluble calcium-comi)onnd, 
fibrin, is formed. Hammarsten, 
on the contrary, is of the opin- 
ion that calcium is carried down 
with the fibrinogen only as a 
contamination, and has no sig- 
nificance in the change of fibri- 
nogen to fibrin, in the presence 
of thrombin. According to his 
theory, the calcium salts are a 
necessary factor only for the 
change of prothrombin into 
thrombin. 

The red thrombus is formed 
under such conditions as the com- 
plete stoppage of the circulation or 
a onarJiCd slowing of the same, and 

comprises the total mass of the red cells (Fig. 14). The precipitated 
fibrin forms granules (Fig. 14, b) and threads («). In fresh clots in 




Fig. 14. — Section through a red thrombus formed in 
one of the veins of the thigh-muscles, after occlusion of 
the femoral vein. (Miiller's fluid; hiematoxyiin.) a. 
Fibrin - threads ; o, leucocytes and granular nuisses. 
X 230. 



THROMBOSIS. 



137 



small vessels, it is not infrequently possible to demonstrate after death, 
by means of special methods, the presence of bundles and star-shaped 
clusters of fibrin- rods (Fig. 13), which radiate from centres of coagula- 
tion. In such cases, however, it is often impossible to distinguish with 
certainty to what extent the coagulation is intravital or to what extent 
post-mortem. Such form of coagulation is most frequently observed in 
inflamed tissues^ and the conclusion is warranted that changes in the 
blood occurj'ing in such inflammatory areas are the cause of this variety 
of fibrio-formation. 

Immediately after its formation the red thrombus is soft and rich in 
the fluids of the blood; later it becomes tougher, denser, and more dry, 
as the flbrin contracts and squeezes out a portion of the fluid. At the 
same time it becomes paler, brownish-red or of a rust-color, inasmuch as 
the blood-pigment undergoes changes similar to those occurring in ex- 
travasations. 

The cause of the ante=mortem intravascular coagulation is to be 

found either in an increase in the production of fibrin-ferment or fihrinogenic 




Fig. 15.— Section from a mixed thrombus rich in 
cells. (Miiller's fluid, hasmatoxylin.) a. Red blood- 
cells; /j, granular masses; c, reticular flbrin con- 
taining many leucocytes; d, threads of flbrin in 
parallel arrangement. X 200. 




Fig. 16.— Section from a white thrombus contain- 
ing but few cells. (Miiller's fluid; ha?matoxylin.) 
a. Granular masses; flbrogranular flbrin form- 
ing a net-like reticulum ; c, flbrln-threads in parallel 
arrangement. X 200. 



substances or in a diminution of the power possessed by the normal vessel-icall 
of inhibiting coagulation. Under certain conditions the more marked ad- 
hesion of the blood to a degenerated area in the vessel-wall may in itself 
be sufficient to induce coagulation. This occurs accordingly in ligated 
vessels, when the endothelium at the point of ligation is injured. It 
takes place, furthermore, when, as the result of the disintegration of 
great numbers of red cells, fibrin-ferment is set free in large amounts 
into the blood-stream — a condition which can be brought about by the 
injection of laked blood, in which the red cells are for the greater part 
destroyed. 

White, mixed, and often distinctly laminated thrombi arise in the 
flowing blood, and consist of masses of yellowish color, or of various 
shades of red, or of alternating layers of red and white. The micro- 
scopical examination shows them to consist of granular and thread-like 
masses (Figs. 15 and 16), leucocytes, and red cells, which in varying -pro- 



138 



DISTURBANCES OF THE CIRCULATION. 



Fig. 1< 



Fig. 18. 



portion and arrangement make up their structure. White thrombi may 
consist almost entirely of granular masses (Fig. 16, a) and fibro -granu- 
lar fibrin, which in some cases is arranged in a mesh work (h), in others 
in fibres running nearly parallel (c) which enclose few leucocytes. In 
other cases the number of cells may be much greater. In mixed thrombi 
(Fig. 15), granular fibrin [h), more rarely hyaline masses, thready 
fibrin (c, d^), and red blood-cells («), in varying x^roportion and in alter- 
nating stratification, constitute the thrombus-mass, and all of these ele- 
ments enclose more or less numerous, often many leucocytes. 

The fibrogranular masses which form part of the structure of the 
thrombus are composed of precipitated fibrin. The gmnidar and hyaline 

masses, on the other hand, 
probably arise directly from 
the products of the plasm= 
oschisis and plasmorrhexis 
of the red blood=cells, in 
particular from the blood= 
plates. In large thrombi 
they often show a coral-like 
arrangement. 

The causes of the forma= 
tion of white and mixed 
thrombi are especially: 
changes in the intima of the 
heart and the vessels and dis- 
eases of the vascular appara- 
tus, which lead to a general 
or local slowing or irregularity 
of the bloodstream. The for- 
mation of tlirombi may be 
studied directly, in suitable 
subjects, under the micro- 
scope, both in the case of 
cold - blooded and warm- 
blooded animals ; and the ob- 
servations made in this line, 
especially by Bizzozero, 
Eberth, Schimmelbusch, and 
Lowit, have led to very im- 
portant results. 

When the blood flows with normal velocity through a blood-vessel, 
there may be seen under the microscope a broad, homogeneous red stream 
in the axis of the blood-vessel (Fig. 17, a), while at the sides there lies a 
clear plasma-zone (b) free from red cells. This may be observed in the 
arteries, veins, and large capillaries, but is best seen in the veins, while 
in the small capillaries, which are just large enough to permit the pas- 
sage of the red cells, tl)is difference between the axial stream and plasma- 
zone is not present. 

In the axial stream the different constituents of the blood-stream are 
not recognizable ; in the plasma-zone there aj^pear, from time to time, 
white blood-corpuscles (Fig. 17, which roll slowly on along the vessel - 
wall. 

If the blood-stream becomes retarded to about the degree that the red 
cells of the axial stream are indistinctly recognizable (Fig. 18, a), the 




Fig. 19. 



Fig. 17.— Rapidly flowing blood-stream, rt. Axial stream: 
b, marginal zone with isolated leucocytes, d. (After Eberth 
and ScHimmelbusch.) 

Fro. 18.— Moderately slow blood-stream, a. Axial stream ; 
ib, periplieral zone with numerous leucocytes, d. (After 
Eberth and Schimmelbusch.) 

Fig. 19.— Markedly slow current, a, Axial stream : 7i, per- 
ipheral stream with blood-plates ; c, collectionof blood-plates ; 
(?, di, leucocj'tes. (After Eberth and Schimmelbusch.) 



THROMBOSIS. 



139 



number of white corpuscles, which roll slowly along in the plasma- zone, 
at times adhering to the vessel -wall, becomes constantly increased (Fig. 
18, d), so that they finally come to lie in great numbers in this zone. 

If the current is still further retarded so that the red cells become 
plainly recognizable (Fig. 19, a), there appear in the peripheral plasma- 
zone, in addition to the colorless blood-corpuscles (d), also blood-plates 
(b), which increase more and more in number with the progressive retar- 
dation of the current, while the leucocytes again become diminished in 
numbers. When total arrest of the blood-current finally occurs, there 
follows a distinct separation of the corpuscular elements in the lumen of 
the vessel. 

If, in a vessel in which the circulation is retarded, the intima is in- 
jured at a certain point by compression or crushing, or by means of 
chemical agents, as corrosive sublimate, nitrate of silver, or sodium 
chloride, and if the lesion of the wall does not lead to a complete stop- 
page of the circulation, blood-plates may be seen adhering to the injured 
portion of the ivall ; and in a short time the injured si)ot is covered with 
many layers of the same (Fig. 19, c). Often, more or less numerous 
leucocytes {dj become embedded in this mass, and their number is the 
greater the more numerous these are in the plasma-zone. Under certain 
conditions they may be very numerous and partly cover up the blood- 
plates. In case of great irregularity of the circulation or more severe 
changes in the vessel -wall, red cells may also drop out of the circulation 
and become adherent to the vessel -wall or the colorless deposit already 
formed, ^ot infrequently portions of the thrombus-mass are again torn 
loose, in which case a new deposit of blood -plates occurs. The vessel 
may finally be closed as the result of a long-continued deposit of the 
blood-elements. 

When at any point blood-plates in large numbers have become ad- 
herent to the vessel-wall, they become after a time coarsely granular at 
their centre, and finely granular or homogeneous at their periphery, and 
become fused together into one compact mass. The final result of this 
process is the formation of a colorless blood-plate thrombus, within which 
more or less numerous leucocytes may be imprisoned. Eberth designates 
the sticking together of the blood-plates as confflutination, their fusion 
into a coherent thrombus-mass as viscous metamorphosis. 

If we compare the observations made upon warm-blooded animals, 
by Bizzozero, Eberth, and Schimmelbusch, and more recently by Lowit, 
with the histological findings in thrombi occurring in the human subject, 
we are warranted in drawing the conclusion that the formation of thrombi 
in the circulating blood of man occurs in part in the same way as that 
observed in the lower animals. Thrombosis is, therefore, directly depend- 
ent upon two causes: namely, disturbances of the circulation, particu- 
larly retardation of the current and the formation of eddies ivhich drive the 
blood-plates against the vessel-wall ; and local changes in the vessel=walls. 
It is also probable that thrombosis is favored by pathological changes in 
the blood. From the variety of conditions under which thrombosis in 
man occurs, wo must assume that at one time one cause, at another time 
another, plays the chief part in the formation of the thrombus, or that 
all three may take an equal part in the process. 

If a blood-plate thrombus or a conglutination-thrombus has formed 
at any point, coagulation may subsequently occur, yielding fibrin-threads 
which enclose a greater or less number — often large numbers— of the 
cellular elements of the blood. Conglutination and coagulation may occur 



140 



DISTURBANCES OF THE CIRCULATION. 



in comhinaiion ; and the frequency with which this coines to pass, judging 
from the composition of the thrombi occurring in man (Figs. 15 and 16), 
seems to denote the fact that fibrin-ferment is i3roduced during the for- 
mation of the blood-phite thrombus, and that consequently, in the neigh- 
borhood of the conglutinated blood-plates, processes of coagulation 
occur in the adjacent plasma-zone of the blood-stream. If white corpus- 
cles alone are circulating in this zone, t he mass of coagulum is white 
(Fig. 16) and encloses a greater or less number of red cells; if red cor- 
puscles also circulate in the peripheral zone, or if the coagulation extends 
into the red axial stream, mixed thrombi will be formed (Fig. 15). 

If in marasmic individuals, as not infrequently happens, or in those 
who have been subjected to some traumatism, extensive thrombosis oc- 
curs, this occurrence is probably connected with a ferment-intoxication 
(Kohler, von During) ; and the local disturbances of circulation only 
decide the location of the coagulation. Yaquez is of the opinion that 
infections play a verj^ prominent role in the origin of cachectic thrombi. 

■ AccordiDg to JSnunyn, Franken, KdJder, Plosz, Gyorgi/ai, Hanau, and others, a 
more or less extensive tlirombosis may be produced by the injection into the blood- 
vessels of laked blood, solutions of haemoglobin, salts of cholic acid, ether and other 
substances; yet the results of this experiment are not constant (.9(7/(7^^7', Ilof/i/e!^. Lan- 
dais, Ebertli), and coagulation may not occur. Tlie probability of effecting coagulation 
is proportionate to the degree of disturbance produced in the blood by the substance 
injected. 

According to Arthus and Pages, the blood flowing from the veins becomes inca- 
pable of coagulating spontaneously, if sodium oxalate, sodium fluoride, or soaps are 
added to it in such quantities that the mixture contains O.OT-0.1 per cent of the oxalate, 
or about 0.3 per cent of the fluoride, or 0.5 per cent of soap. These salts all act by 
precipitating the calcium salts. If to blood, kept fluid by treatment with oxalic acid, 
one-tenth of its volume of a one-per-cent solution of calcium chloride is added, coagu- 
lation occurs in six to eight minutes, and the calcium salts pass into the combination of 
the tibrin-molecule. The flbrin-ferment can act upon the fibrinogen only in the pres- 
ence of calcium salts. Under tlie influence of the flbrin-ferment. and the presence of 
calcium salts, the flbrinogen undergoes a chiMuical change which results in the forma- 
tion of a calcium-compound, fibrin. Ila m imn-sf, n , who holds that the presence of cal- 
cium is not necessar}'^ for the change of fibiinogcn into fibrin, attemiits to explain the 
observation of Arthus ?Ln(\ Fajjes, xlwongh the assumption lhat the calcium salts are 
necessary factors for the conversi(m of prothrombin into thrombin. 

If blood be allowed to flow beneatli a layer of oil. into a vessel coated with a film 
of vaseline, it will not coagulate : and from tins it may be assumed that the 

cause of the coagulation is to be found in the adhesion of the blood to a foreign body. 

B/izozcro, in the year 1882, described as a new element of the blood, small, flat, 
homogeneous structures, which he designated as blood-plates, and regarded as identical 
wuth the hannatoblasts described by ILnit/ui. Supported hy thorough experimental 
investigations, he assumed that it was these bodies, which in breaking up, induced 
coagulation: and, therefore, denied tlii^ to be a propertv of the leucocvtcs. Bmisclien- 
hach, lleyL Wtujcrt. Lnirit. Ebertli, S'liiiunulhnsrJi. lUura. Grotli, and others, have op- 
posed the teaching of Blzzozero, in that they in part o]ipose the causal relation of the 
blood-plates to coagulation, and in part ( b ( /y^^ ^ Ilincd, IlnJId, and Z/i/r/O regard the 
blood-plates not as constant foj'med elements of the blood, but as degeneration-products 
of the colorless blood-corpuscles, or as a product of a precipitation of globulin {Lda-it). 
From their contributions we ma}' also gather that the disintegration of leucocytes in 
fluids containing fibrinogen may give rise to coagulation, so that tlie blood-plates are 
not the only fibrin-formers. According to Grotli, the injection of large numbers of 
leucocytes into the blood-vessels leads to thrombosis. According to ]?i> i/,scJ/( //!>,/ rj/. the 
dissolution of leucocytes is constantly' occurring in the blood; but through the inhibi- 
tory powers of the organism, the fibrin- ferment is rendered inac1i\'e. 

ZaJiii, in 1875, was the first to differentiate strictly between red, white, and mixed 
thrombi. He regarded the colorless substance of the white and mixed thrombi as for- 
mations, arising from colorless corpuscles, which become separated from the axial 
stream, attach themselves to rough places of the vessel-wall, and fuse together to form 
homogeneous or granular masses. Up to a few years ago most authors have accepted 
this view; but there can be no doubt, according to the investigations of Blzzozero, 



THE ORIGIN OF THE BLOOD-PLATES. 



141 



Ijubnitzky, Eherth, Schimmelbusch, and Lowit, that there is also a blood-plate thrombus 
iu the production of which the leucocytes play only a subordinate role, and thai 
the thready fibrin of thrombi also may often contain but very few leucocytes (Fig. 16). 

According to Lowit, the blood-plates are not found in the normal blood, but appear 
only under certain conditions; and represent nothing more than globulin precipitated 
in the form of platelets. For their formation very slight changes in the circulation 
and composition of the blood are sufficient ; and it is therefore difficult to make observa- 
tions of the circulating blood without producing them. It is possible, however, by 
observing the greatest precaution, to demonstrate that the blood circulating in the 
mesentery of the mouse contains no formed elements except the red corpuscles and the 
leucocytes. Changes in the vessel-wall and slowing of the current lead to the precipi- 
tation and deposit of blood-plates upon the vessel-wall; and the blood-plates thus pre- 
cipitated are quickly changed into a substance closely related to fibrin, whereby they 
become soluble with difficulty, swell somewhat, and in part present a granular appear- 
ance. The blood-plate fibrin is in its staining-reactions closely related to thready 
fibrin, so that the production of a blood-plate thrombus is, in fact, a form of coagula- 
tion. In cold-blooded animals, under the same conditions as those leading to the for- 
mation of blood-plates in warm-blooded animals, the globulin is precipitated in a gran- 
ular form, but not in the shape of blood-plates. The small spindle-shaped elements 
found in the blood of cold-blooded animals and in birds, and which have been regarded 
by Bizzozero, Eberth, and ScMmmelhuftch as equivalents to the blood-jDlates, are nothing 
more than young colorless cells, which in part become transformed into ordinary leu- 
cocytes, and in part into red blood-cells. They possess nuclei, and can assume a round 
form, while the blood-plates are non-nucleated, and cannot actively change their form. 
Changes iu the vessel-walls and slowing of the current lead in the case of cold-blooded 
animals to the formation of thrombi consisting essentially of leucocytes, which may 
be converted into granular masses. At the beginning of cell-deposition the spindle- 
shaped leucocytes are often deposited in great numbers. 

The view of Loirit as to the genesis of the blood-plates I cannot accept; I hold 
rather that the blood=plates are products of red blood-cells which are either thrown 
off from degenerating red cells, or are formed by the disintegration of the same. I 
base my opinion upon the investigations wdnch Wlassoic, at my suggestion, carried out 
in my laboratory in 1893. Wlassow studied both the early stages of thrombosis, and 
the behavior of the blood -corpuscles when treated with different fluids. His observa- 
tions would indicate that, on the one hand, in the beginning of thrombosis, in circulat- 
ing blood, the red corpuscles become adherent, undergo changes and are converted into 
a granular mass; that on the other hand, a portion of the red cells (most probably those 
which are the oldest and are approaching their disintegration) are very unstable cells, 
from which there may be easily formed structures which correspond to the blood- 
plates, in so far as their properties are concerned. Whether such structures develop 
under normal conditions, or whether in the normal disintegration of the red cells the 
colorless elements of their cell-bodies pass immediatelj^ into solution, cannot be decided; 
this much only can be demonstrated : that the most diverse influences may cause a 
plasmoschisis of the red cells with formation of the so-called blood-plates. Arnold has 
recently published observations upon the products of the red cells resulting from a 
process of constriction and setting free of portions of the cell; and these confirm and 
extend the observations made by Wlassow and mvself. 

A. Schmidt, in his work on the blood, published in 1892, in which he collects the 
results of many years of study on the coagulation of the blood, regards the fibrin- 
ferment or tliromhiii as a cell -derivative, which arises from an inactive antecedent sub- 
stance, protlirombin, under the influence of certain zymoplastic substances which are also 
cell-derivatives. He likewise regards the fbrinogenic substance or metaglobulin, as a 
product of the disintegration of cellular protoplasm. Therefore, the substances caus- 
ing coagulation as well as those producing thrombosis must all be regarded as cell- 
derivatives, and the red blood-cells in particular are the source of the materials of coag- 
ulation. 

According to Covin, coagulation occurs in the blood of the cadaver only when the fer- 
ment teas present in the blood during life ; and the extent of the coagulation is dependent 
directly upon the amount of ferment contained in the blood during life. A. further 
formation of ferment does not take place after death; on the other hand, it is probable 
that there is formed by the vessel-walls a body inhibiting coagulation. Between the 
blood of those dying suddenly (strangulation), and that of individuals dying slowly, 
there is only a relative difference, depending upon the amount of ferment present. A 
fluid condition of the blood of the cadaver can, therefore, be of no significance in so far 
as the diagnosis of the manner of death is concerned. 



142 



DISTURBANCES OF THE CIRCULATION. 



Literature. 

{Blood -plates J Coagulation of the Blood, and Thrombosis.) 

Arnold: Freie Kiigelthroinben. Beitr. v. Ziegler, viii.. 1890; Biologic der Blutlvorper, 
Virch. Arch., 145 Bd., 1896; Die Hcrkimft der Blutplattclien. Cbl. f. allg. Path., 
viii., No. 8, 1897; Morphologic der extrayasciililreu Gcriunimg. Virch. Arch., 150 
Bd., 1897; Morphologic der intra vase. Geriummg. lb., 155 Bd., 1899; Gerin- 
nimgscentrcn. Cbl. f. allg. Path., 1899. 

Arthus: La coagulation du sang, Paris, 1899. 

Arthus et Pages : Nouvelle theorie chimiqiie de la coagulation du sang. Arch, de 
phys., ii., 1890. 

Aschoff: L^eber den Aufbau der menschl. Thrombeu. Virch. Arch., 130 Bd.. 1892. 
Bavmigarten : Zur Lelire vom rotlien Thrombus. Cbl. L die med. Wiss., 1877: Leber 

die neueu Staudpunkte in der Lehre von der Thrombose. Berl. klin. Woch., 1886. 
Bizzozero: Blutplattchen u. Blutgerinuung. Cbl. f. d. med. Wiss., 1882, 1883; 

Virch. Arch., 90 Bd. ; Arch, per Te Sc. Med., 1883; Arch. ital. de biol., i., ii., iii., iv. 

and xvi. ; Festsclir. f. Vircliow. Internat. Beitr., i., 1891. 
Bottcher: Verhalten d. Blutes in doppelt unterbund. Gefasseu. Beitr. v. Zieo-ler, ii., 

1888. 

Briicke: L'eber die L^sache der Gerinnung des Blutes. Virch. Arch., 12 Bd., 1857. 
B"iich.lers: Autochthone Hirnsinusthrombose. Arch. f. Psych., 15 Bd., 1893. 
Castellino: Xature du zymogene du fibrino-ferment. Arch. ital. de biol.. xxiv.. 1895. 
Corin: Leber die Ursachen cfes Fliissigbleibens des Blutes bei der Erstickung u. and. 

Todesarten. Vierteljalirsschr. f. ger. ]Med., v., 1893. 
V. During: Fermentintoxication u. ihre Bezieh. z. Thrombose. Deut. Zeit. f. Chir,, 

xxii.. 1885. 

Eberth. u. Schimmelbusch. : Die Thrombose nach A'ersuchen u. Leichenbefunden, 

Stuttg., 1888; Dvskrasie u. Thrombose. Fortschr. d. 3Ied., vi., 1888. 
Eisen: Blood-Plates^ Journ. of Morph., xv., 1899. 

Feldbausch: Bed. d. roth. Blutkorp. f. d. Gerinnung. Virch. Arch., 155 Bd., 1899. 
Freund: Blntgerinnung. Limbeck's Pathologic des Blutes, Jena, 1896. 
Halliburton: "The Coagulation of the Blood. British Med. Journ., 1893. 
Hamniarsten : Lehrb. d. phys. Chemie, Wiesbaden, 1899. 

Hauser: Beitr. zur Lehre von der Fibrin gerinnung. Deut. Arch. f. klin. Med., 50 
Bd.. 1892: Gerinnuno-sceutren. Virch." Arch. , 154 Bd., 1898; Cbl. f. allg. Path., 
X., 1899. 

Hayem: Du sang et de ses alterations anatomiques, Paris, 1889. 

Hlava: Bezieh. d. Blutplattchen zur Gerinnung u. Thrombose. Arch. f. exp. Path., 
xvi., 1883. 

liilienfeld: Blntgerinnung. Zeitschr. f. pliys. Chem., xx., 1894. 
V. Limbeck: Klin. Pathologie des Blutes, Jena. 1896. 

Lowit: Blurgerinnung. Sitzber. d. K. Akad. d. Wiss. in Wien, 89, 90 Bd.. 1884; 
Blutplattchen u. Blutgeriummg. Fortschr. d. ]\[ed., iii., 1885; Die Beobachtuug 
der Circulation am Warmbliiter. Arch. f. exp. Path., xxiii., 1887; Blutplattchen 
u. Thrombose. lb., xxiv., 1888 ; Blutplattchen u. Thrombose. Fortschr. d. IMed., 
vi. . 1888; Beziehuno- der weissen Blutkorperchen zur Blntgerinnung. Beitr. v. 
Ziegler, v., 1889; Priicxistenz der Blutplattchen. Virch. Arch., 117 Bd., 1889; 
Cbk f. allg. Path., ii.. 1891; Studieu zur Phvsiologie u. Pathologie des Blutes, 
Jena, 1892. 

Mliller: Die morphol. Veriinderung der r. Blutkorperchen. Beitr. v. Ziegler. xxiii.. 
1898. 

Pekelharing: Bedeutung d. Kalksalze fur die Gerinnung. Festsclir. f. Virchow, 
Berlin, 1891: Lnters. ab. das Fibrinferment, Amsterdamri892 ; Gerinnuusi'. Deut. 
med. Woch., 1892. 

Petrone: Sulla coagulazione del sangue, Morgagni, 1897. 

Sacerdotti: Piastrine del sangue. Arch, per le Sc. Med., xiii., 1893; Anat. Auz., xvii., 
1900. 

Salvioli: Comparticipaz. dei leucociti nella coaa-ulazione. Arch, per le Sc. Med., xix., 
1895. 

Scherer: Zooid- u. Oekoidbildung i. d. rotheu Blutkorp. Zeitschr. f. Heilk., xvii., 
1896. 

Schmidt, A.: Die Lehre v. d. fermentativen Gerinnnngserscheinungeu. Dorpat. 1877; 

Zur Blutlehre. Leipzig. 1892: Weitere Beitnige z. Blutlehre. Wiesbaden. 1895. 
Sclimiedeberg : Elementarformen einia-er Eiweisskorper (Fibrin). Arch. f. exp. Path., 

39 Bd., 1897. 



THE CAUSES OF THROMBOSIS. 



143 



Schmorl: Unters. liber Puerperaleklampsie, Leipzig, 1893. 

Vaquez: De la thrombose cacliectiqiie, Paris, 1890; Des coagulat. sanguines intra- 
vascul., Nancy, 1896. 

ITirchow: Gesamm. Abhandlungen, Frankfurt, 1856, u. Handb. d. spec. Path., i., 
1854. 

Weigert: Pathol. Gerinnungsvorgaage. Vircli. Arch., 79 Bd., 1880; Weisser Throm- 
bus. Fortsch. d. Med., v., 1887. 

Wlassow: Unters. lib. die histolog. Yorgitnge bei der Gerinnung u. der Thrombose 
mit besond. Beriicksicht. der Entstehung der Blutplattclien. Beitr. v. Ziegler, 
XV., 1894. 

"Wooldridg-e : Die Gerinnung des Blutes, Leipzig, 1891. 

"Wrig-ht: Contr. to the Study of the Coagulation of the Blood. Journ. of Path., i., 
1893. 

Zahn: Thrombose. Virch. Arch., 62 Bd., 1875; Rippenbildung an der Oberflache der 
Thromben. Internat. Beitr., Festschr. f. Virchow, ii., Berlin, 1891. 

Zenker: Intra vasculare Fibringerinnung. Beitr. v. Ziegler, xvii., 1895. 

Ziegler: Ueber den Bau der endocarditischen Efflorescenzen. Verh. d. Congr. f. inn. 
Med., vii., 1888; Neue Arbeiten liber Blutgerinnung. Cbl. f. allg. Path., iv., 
1893; Thrombose. Eulenberg's Realencyk., xxiv., 1900 (Lit.). 
See also § 39. 

§ 39. Thrombosis occurs most frequently in cases of degeneration and 
inflammation of the intima of the heart and of the blood-vessels, as well 




Fig. 20.— Thrombus-formation in the heart following flbrold change and aneurismal dilatation of the 
ieart-wall. a. Fibroid thicliening of the endocardium ; b, fibroid areas in myocardium ; c, thrombus. 
(Two-thirds natural size.) 

as under certain conditions which cause a slowing or stoppage of the cir- 
culation — as, for example, compression, narrowing, or dilatation of the 
vessels, fatty heart, stenosis and insufficiency of the valvular orifices, 



144 



DISTURBANCES OF 



THE 



CIRCULATION. 



etc. Perforating wounds of the vessels, crushing of the vessel-wall, and 
laceration of the intima lead likewise to the formation of thrombi ; and 
thrombotic precipitates are formed also upon foreign bodies lying in the 
vessels. According to the cause of the injury to the vessel- wall there 
may be distinguished : traumatic, infectious, and thermic thrombi, as well 
as those produced by degenerative changes in the wall, foreign bodies, and 
tumor proliferation. Thrombi occurring in enfeebled individuals with 
poor circulation (cardiac weakness) are usually designated as marasmic 
or cachectic. 

Thrombi may be classed also according to their relation to the vessel- 
lumen. Thus thrombi attached to the wall of the heart (Fig. 20, c) or 

blood-vessel are known as parietal 
thrombi, those situated upon the valves 
of the heart or veins (Fig. 21, d) are 
termed valvular thrombi. In both 
cases the thrombi may consist only of 
delicate, translucent, membranous, hy- 
aline deposits; but are often thicker 
and firmer and project into the lumen 
of the heart or blood-vessels. Their 
surface often shows ribbed elevations 
which are paler than the other portions. 
A thrombus completely closing the lumen 
of the vessel is called an obturating 
thrombus (Fig. 21, a, b). The coagula 
first formed are designated as primary 
or autochthonous, those subsequently 
deposited upon these as induced throm- 
bi. Through growth by accretion a pa- 
rietal thrombus may become changed to 
an obturating one. In this way it not 
infrequently happens that upon an orig- 
inally white or mixed thrombus a red 
one (Fig. 21, c) is formed; the throm- 
bosis at the beginning occurring in cir- 
culating blood, while later, after the clos- 
ing off of the vessel, the blood stands 
still and clots e7i masse. The reverse 
may occur — that is, ujyon a thrombus 
originally red there may be deposited 
white or mixed coagula — when a red 




€ 



Fig. 21. — Thrombosis of femoral and 
saphenous veins, a, h. Obturating mixed 
and laminated thrombus ; c, red thrombus 
showing peripheral attachment; c?, throm- 
bus protruding from a valve. (Reduced 
one-fourth.) 



coagula- 

thrombus obturating a vessel becomes 



smaller by contraction, and thus opens up 
a channel for the free passage of blood. 
Thrombi may occur in any part of the vascular system. In the heart 
they are formed chiefly in the auricular appendages and in the intertra- 
becular spaces, as well as upon any diseased spot (Fig. 20, &) in the 
heart-wall. They begin usually in the deep recesses between the tra- 
beculie, but through continual accretions they form larger masses of 
coagula which project above the surface in the form of polypoid masses 
(Fig. 20), which are called heart=polypi. They are sometimes more or 
less spherical in shape, with a broad base ; at other times they are more 
club-shaped ; their surface is often ribbed. In rare cases large spherical 
or knobby thrombi may become loosened ; and, in case they cannot pass 



THE FORMATION OF THROMBI. 



145 



the ostium, lie free in the corresponding chamber of the heart. Such 
free globular thrombi are sometimes seen in the auricles in cases of 
stenosis and insufficieucy of the auriculo- ventricular orifices, but they are 
of l ai e occurrence. After their detachment they may increase in size 
through the formation of new deposits of fibrin. Masses of coagula 
which are deposited upon inflamed valves are known as valvular polypi. 
Parietal and v alvular polypi may become very large and fill up a large 
part of the heart- chambers. 

In the arterial trunks thrombi may occur in a great variety of places, 
particularly behind constrictions and in dilatations. Occasionally in 
cachectic individuals with a much- degenerated 
arterial intima, parietal, white, or mixed thrombi, 
adherent to the surface, are formed in the aorta. 

In the veins thrombi are occasionally formed 
in the pockets of the valves (Fig. 21, d), from 
which they may gradually protrude and develop 
into obturating thrombi. Often a thrombus may 
grow from a smaller vein (a), where it was pri- 
mary, into the lumen of a larger vein (b). Thus, 
for example, a thrombus having its origin in a 
small vein of the lower extremities may finally 
grow into the inferior vena cava and even reach 
the heart. Of especial importance, because of 
the resulting local disturbances, are the obturat- 
ing thrombi of the femoral veins, the renal veins, 
the sinus of the dura mater, the venae cavse, and 
the portal veins. 

Thrombosis in the smallest vessels is most 
frequently the result of disease of the surround- 
ing tissues, particularly infectious and toxic in- 
flammations and necrotic processes. The throm- 
bi formed are, for the greater part, hyaline; in 
their composition the colorless elements of the red 
blood-cori)uscles have the chief share, fusing to- 
gether into a homogeneous mass. Nevertheless, 
it may be demonstrated occasionally, by means 
of proper technique (Weigert's staining method), 
that they also contain thready fibrin. Thrombi 
of smaller vessels occur also after burns of the skin 
(Klebs, Welti, Silbermann) and often in cases of 
poisoning^for example, with corrosive sublimate 
(Kaufmann) — and are found especially in the 
smaller vessels of the lung. They frequently 
occur in hemorrhagic infarcts (Fig. 12, a,). 

Thrombi originating in the capillaries may develop also into the efferent 
veins, partly for the reason that through the obturation of numerous 
capillaries the blood flows more slowly into the veins, partly also for 
the reason that disintegrating red cells and blood-plates pass into the 
veins in large numbers. 

The first deposits in the formation of a parietal thrombus consist of 
delicate, translucent, or whitish layers. The fully formed thrombus is 
a i;iather firm, dry mass, firmly adherent to the inner surface, and in 
color and structure varying according to the conditions mentioned above. 
Thrombi, originally soft and moist, undergo in time a process of contrac- 




Fig. 23. — Remains of a 
thrombus of the right femoral 
vein occurring three years 
before death, a. Obliterated 
portion of the vein (the right 
common iliac artery was also 
obliterated); 7), c, d, connee- 
tivertissue cords in the la- 
mina of the vein and Its 
branches ; e, fresh thrombus. 
(Natural size.) 



146 



DISTURBANCES OF THE CIRCULATION. 



tion, and thereby become firmer and more dry. By means of such con- 
traction vessels closed by obturating thrombi may become again opened 
for the passage of the blood. 

In case of marked contraction, the fibrin, blood-plates, and the red 
blood-cells may become changed into a firm mass, which may remain in 




Fig. 23.~Obliteration of a pulmonary artery by connective tissue after embolic plugging of its lumen. 
(Miiller's fluid, haematoxylin, and eosin.) a, Artery wall; b, connective tissue fllliug the vessel-lumen; 
c, d, newly formed blood-vessels. X 4,5. 

this condition for a long time, become firmly adherent to the vessel-wall, 
and finally undergo calcification. This may occur in both valvular 
heart-thrombi and thrombi located in the vessels. The chalky concre- 
tions formed in this manner in the veins are known as phleboliths ; 
those occurring more rarely in the arteries as arterioliths. 

Contraction and calcification are relatively favorable sequelae of 
thrombosis. Much less favorable are the more frequent processes of de- 
generation occurring in thrombi, which are known as simple and as puri- 

form or yellow septic softening. In 
simple softening the central portion of 
the thrombus becomes changed into a 
grayish-red, or gray, or grayish-white 
grumous mass, consisting of disinte- 
grated and shrunken red corj)uscles, 
pigment -granules, and colorless, gran- 
ular debris. If the softening extends 
to the superficial layers, and if there is 
at the same time a certain strength of 
blood-current in the neighborhood of 
the thrombus, the i:)roducts of disin- 
tegration may be swept along into the 
circulation. If thereby larger pieces 
become loosened and transported by 
the blood-stream, arterial emboli will 
be produced (see Fig. 2). 

In the yellow puriform or septic 
softening the thrombus breaks down 
into a yellow, or grayish-yellow, or- 




FiG. 24.— Remains of embolic plugs In a 
branch of the pulmonary artery, n. Con- 
tracted embolus traversed by connective-tissue 
threads : ?j, cords of connective-tissue crossing 
the orifices of branch vessels. (Natural size.) 



THE SEQUELS OF THROMBOSIS. 



reddish -yellow, pus-like, griimous, creamy, and at times foul-smelling^ 
mass, cousisting of pus-corpascles and a large amount of finely -granular 
substance, composed of fatty and albuminous detritus and micrococci. 
This mass acts as a destructive irritant upon the surrounding tissues, 
giving rise to inflammation. As a result the intima becomes cloudy, and 
there arises a purulent inflammation in the media and adventitia, as 
well as in the tissues about the vessel. After a short time all the vascu- 
lar coats become infiltrated and present a dirty-yellow or grayish-yellow 
appearance. A suppurative destruction of the tissues finally results. 
If puriform masses are transported by the blood-stream to other parts 
of the vascular system, they will give rise to metastatic foci of necrosis 
and septic disintegration of the tissues, and purulent inflammation, in- 
volving not only the vessel -wall but also the neighboring tissues. 

The process of puriform softening of a venous or arterial thrombus, 
associated with a purulent infiltration of the vessel -wall, is designated 
thrombophlebitis purulenta or throinbo=arteritis purulenta. The in- 
flammation of the vessel-wall may take its start either in the softening- 
thrombus or in the tissues adjacent to the vessel. In the latter case the 




Fig. 2o.— Embolism of an intestinal artery, with suppurative arteritis, embolic aneurism, and peri- 
arterial, metastatic abscess. (Alcohol, fuchsin.) a, 5, c, d, e. Layers of the intestinal wall ; /, artery wall ; 
gembolus, surrounded by pus-corpuscles, lying in the dilated artery which is partly destroyed by suppura- 
tion^ panetal thrombus ; i, periarterial purulent infiltration of the submucosa ; 7i-, veins gorged with 



softening of the thrombus is coincident with the inflammation of the ves- 
sel-wall or else follows it. These processes occur most frequently in the 
neighborhood of purulent foci. 

The most favorable sequela of thrombosis is the organization of the 
thrombus— that is, a substitution of the thrombus by vascularized 
connective tissue. 

The new connective tissue develops, in the first place, from the pro- 
liferation of endothelial cells. If these have been destroyed in the for- 



148 



DISTURBANCES OF THE CIRCULATION. 



matioii of the thrombus, the process of orgaiiizatiou is brought about by 
formative cells which wauder iu from the outer layers of the vessel-wall. 
The thrombus itself takes uo part iu the orgauizatiou ; it is a dead mass 
which excites iuflammatiou iu the surrouudiug tissues. Iu the course of 
time the dead thrombus-mass is replaced by vascularized conuective tissue 
(Fig. 23, h, c, d). 

The cicatricial tissue formed iu the place of the thrombus contracts 
more or less iu the course of time. The cicatrices formed after ligation 
may thus become very small. Such a cicatrix iu the continuity of a ves- 
sel may later appear simply as a thickening of the vessel-wall, or there 
may remain only threads and trabeculie (Fig. 22, c, d), which cross 
the lumen of the thrombosed vessel, so that the blood-stream can once 
more pass the affected spot. ^N^ot infrequently tlie connective-tissue 
strands crossing the vessel cause a marked narrowing of the lumen ; or 
the vessel may become completely obliterated (Fig. 22, a), so that the 
vessel for a greater or less distance becomes converted into a solid fibrous 
cord. 

The pieces broken loose from a thrombus and carried into an artery 
and there lodged — that is, emboli — generally induce new deposits of 
fibrin upon their surface. Later they undergo the same changes as 
thrombi, and may either soften, or contract (Fig. 24, a), or become calci- 
fied. If the emboli are non-infective they usually become replaced by 
vascular connective tissue (Fig. 23, b, c). 

In many cases the new-formation of conuective tissue leads to the ob- 
literation of the artery (Fig. 23). In other cases iu the place of the em- 
bolus there is developed only a ridge of connective tissue or a nodular or 
flat thickening of the intima. In still other cases the lumen of the vessel 
is traversed by strands of connective tissue (Fig. 24, h), which either run 
separately or, interlacing, form a fine- or coarse-meshed network. 

If pyogenic organisms are present iu the emboli, as is very likely to 
be the case when the emboli arise from a thrombus lying in a suppurat- 
ing focus, there is produced a purulent process (Fig. 25, i) at the site of 
the embolus (Fig. 25, g), and occasionally ulceration also. 

Literature. 

(Throvd)osis.) 

ApoIIonio: Organisation des Unterbindungstlirombus. Beitr. v. Ziegler, iii., 1888. 
Arnold: Die Gescliicke d. Leukocyten bei der Fremdkorperembolie. Vircli. Arch., 
18;^, Bd., 1898. 

Baumg-arten : Die sog. Organisation des Thrombus, Leipzig. 1877. 

Bubnoff: Ueber die Organisation des Thrombus. Virch. Arch., 44 Bd., 1868. 

Biichlers: Autochthone Hirnsinusthrombose. Arch. f. Phys., 25 Bd., 1893. 

Flexner: Agghitination Thrombi. Jour, of Med. Research. 1902. t 

Herz: Leber altere Thromben im Herzen. Deut. Arch. f. klin. Med., 37 Bd., 1885. 

Heuking u. Thoma: Susbtitut. d. marant. Thrombus durch Bindegewebe. Virch, 

Arch., 109 Bd., 1887. 
Justi: Hyaline Capillarthrombose. Inaug. -Diss., Marburg, 1894. 

Lubnitzky: Die Zusammensetzung des Thrombus in Arterienwunden. Inaug. -Diss., 

Bonn, 1885. 
Osier: Trans, of Assn. Amer. Phys., 1887. 

Pernice: Sulla fusione purulenta del trombo. Sicilia Med., 1., Palermo, 1889. 
Pick: Hyaline Thrombose. Virch. Arch., 188 Bd., 1894. 

E-aab: Anat. Vorgiinge nach Unterbiudung der Blutgefasse. Virch. Arch., 75 Bd.. 
1879. 

V. Recklinghausen: Freie Ku^elthromben. Deut. Arch. f. klin. Med., 37 Bd., 1885. 



STASIS. 



149 



Schweizer: Thrombose bei Chlorose. Virch. Arch., 152 Bd., 1898. 
Stang-e: Kiigelthrombus im Vorhof. Arb. a. d. path. Inst, zu Gottiugen, 1889. 
Vaquez : De la thrombose cachectique, Paris, 1890. 
Virchow: Thrombose und Embolic, Gcs. Abliandl., Frankfurt, 1856. 
Volker: Varix d. Vena facialis ant. mit zwei Venensteinen. Deut. Zeitschr. f. Chlr., 
28 Bd. 

Watson: Boston Med. and Surg. Jour., 1894. 

Welch: Thrombosis and Embolism. Allbutt's Sj^stem of Medicine, 1899 (Lit.). 
Welch, and Flexner: Jour, of Exper. Med., 1896. 
See also § 38. 

§ 40. As stasis or stagnation of the blood is designated a stoppage 
of the circulation without coagulation, in which condition the red blood - 
cells are so closely pressed together that the small vessels appear filled 




Fig. 26.— Congestive stasis m the vessels of the corium and papillae of the plantar surfaces of the 
toes from a man dying of valvular disease, heart failure, and arteriosclerosis. (Miiller's fluid, alum car- 
mine.) Toes presented a deep violet color, and beginning gangrene. X 20. 

with a red mass of blood, in which the outlines of the individual red 
blood-cells cannot be distinguished (Fig. 26). The cause of this condi- 
tion lies most frequently in the occurrence of a ms>r^ed passive congestion. 
When the blood entering into a certain tissue-area finds no avenue of 
exit, the circulation in the small veins and capillaries, and even in the 
smallest afferent arterial branches, comes to a permanent standstill. 
Since from the arteries there come with every pulse-wave fresh masses of 
blood to the congested area, the capillaries and veins become more and 



150 



DISTURBANCES OF THE CIRCULATION. 



more distended and the pressure within these rises to the height of that 
at the point of divergence of the nearest permeable artery. In this way 
a large portion of the fluids of the blood are pressed out of the capillaries 
and veins, and as a result of this the red blood -cells become so closely 
packed together that their contours are no longer distinguishable, and 
the total contents of the vessel form a homogeneous, scarlet-red column 
(Fig. 26). The red blood-cells, however, are not fused together; as soon 
as the hindrance to the outflow is removed and the circulation restored, 
the individual corpuscles become once more separated from one another. 

Stasis may be caused by many injurious influences which affect the 
vessel -wall and the blood itself. Thus, for example, heat and cold, irri- 
tation tvith acids and alkalies, action of concentrated solutions of sugar aiid salt, 
action of chloroform, alcohol, etc. , cause not only contraction or dilatation 
of the vessels and disturbances of circulation, but also under certain 
conditions produce stasis. These injurious agents act in the first place 
by abstracting water from the blood and vessel-walls, and further by 
producing essential changes in the composition of the blood-corpuscles, 
blood-plasma, and vessel-walls ; so that the red cells become less mobile 
and the vessel -walls come to offer increased frictional resistance to the 
blood-stream, and at the same time to permit the fluid portions of the 
blood to pass through them the more readily. Stasis may also be pro- 
duced by loss of water and drying of the tissues, an event which may oc- 
cur, for example, in injuries which lay bare tissues lying within the body 
(intestine). 

Literature. 

(Stasis.) 

Cohnheim: Vorlesimgen fiber allgemeine Patbologie, Berlin, 1882. 
V. Recklinghausen: Allgem. Patliologie d. Kreislaufs u, d. Ernalirnng, Stuttgart, 
1888. 

IV. (Edema. 

§ 41. The free fluid which permeates the tissues is essentially a tran- 
sudate from the blood, though under certain conditions a portion of the 
tissue-fluids contained in the cells and fibres may also pass over into the 
free lymph. The passage of fluid from the vessels is not a simple proc- 
ess of filtration, but is rather to be regarded as of the nature of a secre- 
tion, accomplished by means of a specific function of the capillary walls. 
The fluid secreted by the capillaries mingles with the products of metabo- 
lism in the tissues, and is taken up from the tissue-spaces by means of 
the lymph -vessels, and through the thoracic duct is again returned to the 
venous blood. 

Every increase in the transudation of the fluids of the blood causes 
first a more marked saturation of the tissues, which may be compensated 
for by an increased absorption through the lymph-vessels. This com- 
pensation has, however, its limits ; with increased transudation from the 
blood-vessels there is produced a more or less permanent over-saturation 
of the tissues with the transuded fluids. 

The condition which is produced by this collection of fluids in the tis- 
sues is known as dropsy, oedema, or hydrops. According to the extent 
of the condition there may be distinguished a general and a localized hy- 
drops. An oedema extending over the superficial portions of the body is 
known as anasarca or hyposarca. 



CEDEMA. 



151 



The transudate from the blood ivhich constitutes the oedema or the hydrops is 
always much poorer in albumin than the blood-plasma. The fluid collects at 
first ill the tissue-spaces as free tissue-fluid, but may also soak into the 
tissue-elements themselves and cause a swelling of the cells and fibres, and, 
under certain conditions, the formation of vacuoles (Fig. 27), due to the 
collection of drops of fluid in the cells or their derivatives. 

This may be most frequently demonstrated in the epithelium of the 
body-surfaces and of glands, but becomes at times distinctly evident 
in other tissue-elements — for example, in connective -tissue cells and 
muscle-fibres (Fig. 27), whose fibrillse become iDushed apart by drops of 
fluid. Moreover, it often happens in oedematous tissues that cells be- 
come loosened from their basement-membrane, particularly in the lungs 
and serous membranes, where the epithelial cells in large number may 
be mixed with the fluid. 

Tissues which are the seat of oedema appear swollen, though the de- 
gree of swelling depends essentially upon the structure of the afl'ected 
tissue. The skin and the subcutaneous tissue are able to take up into 
their lymph-spaces large quantities of fluid, so that an extremity may 
become enormously swollen through oedema. In this condition it is pale, 
possesses a doughy consistence, and 
pits on pressure. On incision an 
abundance of clear fluid escapes, 
revealing the tissues thoroughly 
saturated with fluid. 

The lung behaves in a similar 
way. Owing to its limited room 
it cannot become greatly distended, 
but it contains great numbers of 
cavities filled with air, which, in 
the advent of oedema, become filled 
with fluid, which on pressure escapes from the cut surface, generally 
mingled with air-bubbles. 

(Edematous swellings of the kidney, which may become very marked, 
are caused especially by the retention in the dilated urinary tubules of 
the water of the urine secreted by the glomeruli. In the connective tissue 
between the tubules large amounts of fluid collect but rarely. 

The amount of blood contained in oedematous tissues is variable, and 
their color varies accordingly. 

Body-cavities which are the seat of a dropsical effusion contain at one 
time a large, at another time only a small amount of a clear, usually 
light -yellow, rarely quite colorless, alkaline fluid, which at times con- 
tains a few fibrin flakes (see the chapter on Inflammation). Compressi- 
ble organs are compressed by the effusion, the body-cavities are dilated. 

A collection of fluid in the abdominal cavity is known as ascites. 

The albumin-content of pure transudates is not the same in all the 
body-cavities and tissues, but differs in a pronounced degree. Accord- 
ing to Eeuss, the albumin -content of transudations of the pleura is 22.5 
pro mille ; that of the pericardium, 18.3 ; of the peritoneum, 11.1 ; of the 
subcutaneous connective-tissue, 5.8; of the cavities of the brain and 
spinal cord, 1.4. These facts may be taken as a proof of the different 
constitution of the vessel-walls in the various tissues of the body. 

The water of the organs and tissues, according to Heidenhain (" Yersuche und Fra- 
gen zur Lehre von der Lyraphbildung," Arch. f. d. ges. Phys., 49 Bd., 1891, and Yerh. 
10 




Fig. 27.— Longitudinal section of oedematous 
muscle-flbres from the caLE muscles in a case of 
chronic oedema of the legs. (Flemming's solution, 
safranin.) X 45. 



152 



DISTURBANCES OF THE CIRCULATION. 



des X. intemat. med. Cong., ii., Berlin, 1891) consists of three parts — the water of the 
blood present, the lymph of the organ under consideration, and the water contained in the 
cells and fibres — the tissue-water. Under certain conditions the last-mentioned may 
undergo considerable variation, and can increase at the expense of the free water of the 
blood or lymph, or diminish in tlieir favor. 

If the proportion of crystalloid substances (urea, sugar, salts) in the blood be in- 
creased, both the blood and lymph become at the same time richer in water; and this 
is possible only in that the substances injected into the blood pass into the lymphatics, 
and, by their affinity for the tissue-water, excite a passage of Avater from 'the tissue- 
elements. The rapid passage of the crystalloid substances from the blood into the 
lymph is accomplished Avith the aid of a "force inherent in the capillary cells, and is not 
a simple diffusion-phenomenon. This is evident by the fact that the content of the 
lymph in sugar or salts is often greater than that of the blood. 

§ 42. According to tlieir etiology we may distinguish four varieties 

of oedema: oedema from stagnation of the blood ; oedema caused by a Jiin- 
drance to the outflow of the lymph ; oedema caused by disturbance of the cajyil- 
lary secretion due to changes in the capillary walls ; and cedema ex vacuo. 
The third one of these varieties is designated by the practising physician 
as inflammatory, hydrsemic or cachectic, or neuropathic oedema, accord- 
ing to the clinical features of the case. 

(Edema due to stagnation of the blood arises when, as a result of 
the marked hindrance to the outflow of blood from the capillaries, the 
pressure in the capillaries rises and the fluid portion of the blood seeks a 
lateral outlet, so that an increased amount of fluid escapes from the ves- 
sels. The amount of the escaped fluid is the larger the greater the de- 
gree of discrepancy between inflow and outflow ; it is therefore increased 
through a coincident increase of the blood inflow. 

The escaping fluid is always poor in albumin, but with increased 
pressure in the veins the albumin-content is increased (Senator) ; the 
fluid may contain also a greater or smaller number of red blood-cells, the 
number being increased in proportion to the degree of stagnation. 

The immediate result of an increased transudation from the blood- 
vessels is an increase in the lynii)h-flow, and this may be suflicient to 
carry off all the fluid. If it does not so sufflce, the fluid collects in the 
tissue-spaces and there results the condition of stagnation -cedema or 
dropsy. According to Landerer, this occurrence is favored esiDecially by 
the fact that the elasticity of the tissues becomes diminished as the result 
of the long-continued increase of the pressure to which they are sub- 
jected. 

Obstruction to the outflow of lymph, as experiments in this direc- 
tion have shown, is not ordinarily followed by cedema. The lymph- 
vessels in the different regions of the body possess such extensive anas- 
tomoses that an obstruction to the outflow of lymph does not readily occur. 
Even when all of the lymph- channels of an extremity are obstructed, if 
the amount of lymph formed is normal there results no oedema, inasmuch 
as the blood-vessels are able to take up the lymph again. Only the 
occlusion of the thoracic duct is likely to lead to a stagnation of the lymph 
and the production of oedema, particularly of ascites, but it must be ob- 
served that even in this case collateral channels may be opened up and 
sufiice to carry off the lymph. 

Although lymphatic obstruction is not ordinarily suflicient in itself to 
produce oedema, yet it does increase an cedema caused by an increased 
transudation from the blood-vessels. 

Pathological changes in the walls of the capillaries and veins of 
such a nature as to cause an increase in the vascular secretion, and 
thereby give rise to an oedema, may occur as the result of a long-contin- 



CEDEMA. 



153 



ued passive congestion and the consequent imperfect renewal of the blood. 
Such changes occur, however, much more frequently as the result of 
prolonged ischcemia, lack of oxygen, action of Ugh or low temperatures, 
traumatic injury, infection, and intoxication. It is also probable that either 
irritation or xjaralysis of the vasomotor nerves ma^^j lead to an increase of the 
vascular secretion. Just what changes the vessels suffer under these 
conditions we are not able to state precisely, but it may be assumed that 
some alteration of the endothelial cells and of the cement-substance plays 
the chief role. The oedemas produced by the influences above-mentioned 
may be classed according to their cause as toxic, infectious, thermal, 
traumatic, ischasmic, neuropathic, etc. ; and such a classification has 
much to commend it. Hitherto the forms of oedema here under consid- 
eration have been classed ordinarily into two groups — namely, inflam- 
matory and cachectic oedema. 

Inflammatory oedema is without doubt to be referred to an altera- 
tion of the vessel -wall, and occurs both as an independent affection, in 
the forin of circumscribed or more diffuse swellings and hydropic effu- 
sions, and also as a coincident phenomenon in the neighborhood of severe 
inflammatory processes. In the latter case it is frequently designated 
collateral cedema. Inflammatory oedema is distinguished from stagnation- 
oedema by the fact that the transuded fluid is markedly richer in albumin 
and in the number of tvhite blood-corpuscles present, and, further, in the fact 
that larger masses of coagula occur in it (see chapter on Inflammation). 
Its cause is to be sought sometimes in infectious and toxic, sometimes in 
thermal and traumatic influences, at other times in a temporary ischsemia. 

As to hydrsemic or cachectic oedema, it was formerly believed that 
hydrsemia — that is, the diminution of the solid elements of the blood — 
as well as hydrsemic plethora — that is, a retention of water in the blood 
— could directly cause an increased transudation from the blood-vessels. 
It was supposed that the vessel-walls behaved as dead animal mem- 
branes, and allowed a fluid poor in albumin to filter through more easily 
than one richer in albumin. The vessel-wall is not, however, a lifeless 
animal membrane, but must be regarded as a living organ. An hy- 
drseniia experimentally produced does not, according to Cohnheim, give 
rise to an oedema. Even when an hydrsemic plethora is produced by the 
over-filling of the blood-vessels with a watered blood, and there results 
an increased transudation from the vessels, eventually leading to oedema, 
the oedema so produced occurs only when the proportion of water in the 
blood becomes very high, and does not develop in the same regions where 
the so-called hydrsemic oedema in man appears. AVe must therefore as- 
sume that the oedema of cachectic individuals, as well as that occurring 
in individuals suffering from nephritis with impairment of renal func- 
tion, depends essentially upon an alteratioyi of the vessel-wall, which is 
caused either by the hydrsemic character of the blood or by a poison cir- 
culating in the blood. Probably other lesions of the tissue through 
which the elasticity of the tissue is diminished are also concerned (Lan- 
derer). Hydrcemia therefore /a vo/^s the occurrence of oedema, but is not the 
sole cause thereof, and, in particular, does not determine its localization. 

Hydrsemic oedema is distinguished from inflammatory by the fact 
that the fluid is less rich in albumin and contains hnt few corpuscular ele- 
ments. 

(Edema ex vacuo occurs chiefly in the cranial cavity and in the spinal 
cord, and arises in all cases in which a portion of the brain or spinal cord 
is lost and not replaced hj some other tissue. In atrophy of the brain 



154 



DISTURBANCES OF THE CIRCULATION. 



and spinal cord the subarachnoidal spaces in particuhir become enlarged, 
occasionally the ventricles also. Local defects become filled either by a 
dilatation of the nearest subarachnoidal spaces or of the adjacent por- 
tions of the ventricles, or through a collection of fluid at the site of the 
defect itself. 

According to CohnJieim and LicMheim, injections of aqueous solutions of salt into 
the vascular system of dogs {Vircli. Arch., 69 Bd.) show that hydrsemia does not pro- 
duce oedema. If the mass of the fluids of the blood be increased, there results an in- 
crease of almost all the secretions (saliva, intestinal juices, bile, urine, etc.), and also of 
the flow of the lymph ; the latter, however, not universally, in particular not in the 
extremities. In a high degree of hydrsemic plethora the abdominal organs become 
dropsical, but never the extremities. Control-experiments recently carried out by 
Francotte confirm the observation that hydrsemic plethora artificially produced in ani- 
mals causes in the first place a dropsy of the abdominal organs; but this observer was 
able to produce also an a?dema of the skin and subcutaneous tissues. 

The view that the so-called hydraemic oedema is merely the result of an increase in 
the absolute amount of water in the blood, is championed especially by von Reckling- 
Imusen and by Pisenti. The distribution of the dropsy is, according to wn Reckling- 
hausen, essentially dependent upon bodily position, external pressure, impeded circula- 
tion, difference in the innervation of different vascular areas, and the consequent 
difference in the fulness of their vessels. 

I can subscribe to these opinions only in so far as they apply to the influence of 
the above-mentioned modifying factors upon the distribution of the oedema, but not 
as regards the main point. For the other side speak not only the experiments 
of Cohnheim and Lichtheim above mentioned, but also the fact that in nephritic and 
cachectic individuals redema not infrequently appears at a time when no hydraemic 
plethora is present ; and, further, in cases of hydraemic plethora no oedema may occur. 
I therefore look upon the increase in the amount of water as only one factor which is 
favorable to the occurrence of oedema. 

According to the investigations of Pickhardt, pathological transudates constantly 
contain uric acid: the fluid of ascites about 0.0086 per cent; the fluid of oedema, 0.0075 
per cent; and pleuritic exudates about 0.0015 per cent. Sugar is also constantly pres- 
ent, usually as dextrose. 

Effusions into the large serous cavities of the JcrZ?/ occasionally present a milky appear- 
ance, or a certain degree of opalescence. This phenomenon is most often due to the 
presence of chyle {hydrops chylosus), or of fat {hydrops adiposus or chyliformis), or of 
both. Moreover, the presence of different albuminoid bodies, mucoid substances 
{Hammarsten), casein-like bodies {Lion), lecithin {Mitchell, Mattiroli, Gross), may pro- 
duce cloudiness of the transudate. In so far as chyle is not the cause, the substances 
producing the cloudiness arise for the greater part from disintegrating cells. 

According to Heidenhain, the specific function of the capillary walls plays a con- 
trolling part in the formation of the lymph. Consequently, the lymph-production can 
be influenced by various substances present in the blood. The crystalloid substances 
are quickl}^ eliminated from the capillaries, and cause a discharge of tissue-fluid into 
the lymph, as has already been mentioned in § 41. Heidenhain has, however, found 
substances which, when injected, cause an increase In the transudation of water from 
the blood into the lymph. This may be accomplished, for example, with decoctions of 
the muscles of crabs and of fresh-water mussels, or of the heads and bodies of leeches, 
or through injections of peptone and egg-albumen. By these means the amount of 
lymph flowing from the thoracic duct may be increased five-, six-, and fifteenfold. At 
the same time the amount of organic constituents in the lymph is increased. The 
active substances must therefore stimulate the specific function of the cells of the 
vessel-walls which secrete the lymph. According to these observations, it is probable 
that many of the affections of the skin described as neuropathic, and which are charac- 
terized by hyperaemia associated with cedematous swelling — as, for example, urticaria, 
erythema nodosum, herpes zoster — are to be regarded as symptoms of intoxications 
coupled with nervous affections and with disturbance of the secretory activity of the 
capillaries. It is also possible that the secretion of the capillaries may be directly af- 
fected by nervous influences. 

Asher and Barhera hold the view that the regulation of the transudation-process 
takes place not through the capillary walls, but through the vital activity of the tissue- 
cells. 

Magnus, on the other hand, on the ground of experimental investigation (infusions 
of physiological salt-solutions in normal animals, irrigation of dead animals after poi- 
soning with arsenic, chloroform, chloral hydrate, and ether, and after the removal of 



CEDEMA. 



155 



the kidneys and ligation of the ureters), arrives at the following conclusions: The capil- 
lary walls during life offer a resistance to the passage of fluids; after death this resist- 
ance disappears. An injury to the capillary wall, and a diminution of its resistance, 
favor the occurrence of oedema. There are poisons which are able to injure the capil- 
lary-wall in such a manner that it becomes abnormally permeable. 



Literature. 

{(Edemu: Effusions into the Body -Cavities.) 

Asher u. Barbera: Eigensch. u. Entstehung d. Lymphe. Zeit. f. Biol., 1897. 
Barg-ebuhr: Chylose Ergiisse in der Pleura. Deut. Arch. f. klin. Med., 54 Bd., 1895 
(Lit.). 

Bernheim: Beitr. z. Chemie der Exsudate u. Transsudate. Virch. Arch., 131 Bd., 
1893. 

Boddaert: Developp. de I'oedeme. Ann. de la Soc. de med. de Gand, 1893; (Edeme 

lymphatique. Acad. Roy. de med. de Belgique, 1895. 
Citron: Eiweissgehalt u. spec. Gewicht pathol. Fliissigkeiten. Deut. Arch. f. kl. 

Med., 46 Bd., 1890. 

Cohnbeim : Allgem. Pathologic, 1882; Untersuch. ill), d. embolischen Processe, Ber- 
lin, 1872. 

Cobnbeim u. Licbtbeim: Ueber Hydramie u. hydramisches ffidem. Virch. Arch., 
69 Bd., 1877. 

Cobnstein: Transsudation u. Lymphbildung. Virch. • Arch. , 135 Bd. ; Pfluger's 
Arch., 59 Bd., 1894; CEdem u. Hydrops. Ergebn. d. allg. Path., iii., Wiesbaden, 
1897 (Lit.). 

Emmingbaus : Abhangigkeit d. Lymphabsonderungen v. Blutstrom. Arb. d. phys. 

Aust. zu Leipzig, viii., 1874. 
Francotte: De I'oedeme hydremique. Bull, de I'Acad. Roy. de med. Belgique, ii., 

Bruxelles, 1888. 

Gross: Pseudochylose Ergusse. Arch. f. exp. Path., 44 Bd., 1900. 
Grossmann: Muscarinlungenodem. Zeitsclir. f. klin. Med., xii., 1887. 
Halliburton: Chemische Physiologic u. Pathologic, Heidelberg, 1893. 
Hamburg-er: Hydrops von mikrobiellem Ursprung. Beitr. v. Ziegler, xiv., 1893. 
Hammarsten: Mucoidsubstanzen in Ascitesfllissigkeit. Zeit. f. phys. Chem., xv., 
1891. 

Heidenbain: Zur Lehre von der Lymphbildung. Verhandl. d. X. internat. med. 

Congr., ii., Berlin, 1891; Arch. f. d. ges. Phys., 49 Bd., 1891. 
Klebs, A.: (Edem d. Hornhautepithels. Beitr. v. Ziegler, xvii., 1895. 
Landerer: Die Gewebsspannung, Leipzig, 1884. 

Lassar: Ueber (Edem u. Lymphstrom bei der Entziindung. Virch. Arch., 69 Bd., 
1877. 

Lazarus: The Pathol, of (Edema. Brit. Med. Journ., i., 1895. 

Leydbecker: Carcinom d. Duct, tlioracicus mit chylosem Ascites. Virch. Arch., 134 
Bd., 1893. 

Lion: Ascite laiteuse non cliyleuse. Arch. d. med. exp., xv., 1893. 

Lowit: Entstehung d. Lungenodems. Beitr. v. Ziegler, xiv., 1893; Lungenodem, 

Cent. f. a. Path., 1895. 
Lukjanow: Allgem. Pathologic des Gef assy stems, Leipzig, 1894. 
Mag-nus: Entstehung d. Hautodeme bei hydr. Plethora. Arch. f. exp. Path., 42 Bd., 

1899. 

Munk: Transsudate. Eulenburg's Realencyklop., xxiv., 1900. 
Pickardt: Zur Chemie patholog. Ergusse. Berl. klin. Woch., 1897. 
Pisenti: Beitrag zur Lehre von den Transsudaten. Cbl. f. allg. Path., ii., 1891. 
duineke: Hydrops chylosus u. adiposus. Deut. Arch. f. klin. Med., 6 Bd. ; Ascites, 
lb., 30 Bd. 

V. Recklingbausen : Handb. d. allg. Path. d. Kreislaufs u. der Ernahrung, Stutt- 
gart, 1883. 

Reuss: Verhaltn. d. spec. Gew. z. Eiweissgehalt in serosen Fliissigkeiten. Deut. 
Arch. f. klin. Med., 28 Bd. ; Beurtheilung von Exsudaten und Transsudaten. 
lb., 24 Bd. 

Senator : Ueber Transsudation und liber den Einfluss des Blutdrucks, auf die Beschaf- 
fenheit der Transsudate. Virch. Arch., Ill Bd., 1888; Ascites chylosus u. Chylo- 
thorax bei Carcinom d. Ductus thor. Cbl. f. inn. Med., 1896. 

Starling: On Absorption from and Secretion into the Serous Cavities. Joum. of 



156 



DISTURBANCES OF THE CIRCULATION. 



Phys. , xvi., 1894 ; The Influence of Mechanical Factors on Lymph Production. lb., 
1894; Action of Lyniphagogues. lb., xvi., 1894; Absorption of Fluids by Blood- 
vessels, lb., 1896; The Causation of Dropsy. Lancet, 1896. 
Tchirkoflf: CEdemes vasomoteurs. Rev. de med., xv., 1895. 
See also § 46. 



V. Haemorrhage and the Formation of Infarcts. 

§ 43. By haemorrhage is understood the escape of all the constituents 
of the blood from the vessels (extravasation) into the tissues or upon a 
free surface. It may be either arterial, venous, or capillary, or the blood 
may escape from the heart. The blood which has escaped from the vas- 
cular system is termed an extravasate. For the designation of especial 
forms of hsemorrhage a very great variety of terms is used. If the 
hsemorrhagic foci are small, and form more or less sharply outlined, 
punctate, red or dark-red spots, they are called ^^tec/iia? or ecchymoses ; 
if they are larger and not sharply outlined, they are known as suggiUa- 




FiG, 38. — Hgemorrhage in the skin near the knee; from a man eighty-one years of age. (Formalin, 

htematoxylin, and eosin.) X 80. 

tions and as bloody suffusions. If the affected tissue is firmly infiltrated 
with the escaped blood, but not torn or destroyed, the condition is spoken 
of as a hcemorrhagic infarct. If the extravasated blood forms a large 
mass, this is known as a hcematoma or hlood-tumor. 

The blood which escapes from the vessels into the tissues collects at 
first in the tissue-spaces (Fig. 28). Large haemorrhages may completely 
conceal the structure of the tissue. Delicate tissues, as those of the brain 
or spinal cord, may be destroyed by large haemorrhages. 

If the hsemorrhage occurs on the free surface of an organ, the blood 
either escapes externally or is poured into a neighboring cavity. 

Haemorrhage from the nose is called epistaxis ; vomiting of blood, 
hoematemesis ; bleeding from the lungs, hcemopto'e or hcemoptysis ; from the 
uterus, metrorrhagia and menorrhagia (during the menses) ; haemorrhage 
from the urinary organs, hcematuria; hemorrhage from the sweat-glands, 
hcematidrosis. 



HEMORRHAGE. 



157 



A collection of blood in the uterine cavity is designated as hmnato- 
rneU a, in the pleural cavdty as hcemothorax, in the tunics of the testicle as 
hcemaiocele, in the pericardium as hcemopericardium. 

Htemorrhages of the skin not caused by trauma are usually termed 
purpura (Fig. 28). Collections of blood and fluid beneath the ei3idermis 
in the place of the loosened decider ei^ithelial layers give rise to hwmor- 
rhagic hlehs. 

Eecent extravasations show the characteristic color of either arterial 
or venous blood. Later the extravasate shows various alterations which 
are characterized particularly by color-changes. Suggillations of the 
skin become first brown, then blue, and green, and finally yellow. In 
the course of time the extravasate is absorbed (see Chapter V. ) , and dur- 
ing this absorption tissue-proliferation often occurs. Large collections 
of blood may become partly organized into connective tissue or may 
become encapsulated (see Chapter YIL). 

A haemorrhage may occur, in the first place, from rupture of the 
heart or the vessel=wan — that is, per rhexin or per diabrosin. This is 
the only form of cardiac and arterial hemorrhage. From the capillaries 
and veins hiemorrliage may occur also per diapedesin — that is, by a proc- 
ess. in which the red cells escape through the vessel-wall without the oc- 
currence of a tear in the same. Very often such haemorrhages are small 
and of slight extent ; in other cases the process continues for a longer 
time, and the infiltration of the tissues with red cells reaches a significant 
degree. Haemorrhages by diapedesis are tlierefore not always small, 
haemorrhages by rhexis not always large. The rupture of a capillary 
or small vein does not give rise to a large haemorrhage ; on the other 
hand, a haemorrhage through diapedesis can reach an important size. In 
a given case it is not always easy, and often impossible, to decide whether 
the haemorrhage has arisen through rhexis or diapedesis. 

The phenomenon of diapedesis may be observed under the microscope in the frog's 
mesentery or in the web of its foot. If before the examination the efferent veins are 
ligated, the capillaries and veins are seen to be engorged with blood. After a certain 
time the red cells pass from the capillaries and veins (see Cohnheim, " Allgem. Pathol.," 
i., and Virch. Arch., 41 Bd.). Hering (Sitzungber. d. Wiener Akademie, 1868, Bd. 57) 
regards the phenomenon as a filtration-process. As a result of the obstruction to the 
OLittiow the blood seeks to escape laterally, and is forced through the vessel- wall. 

Exhaustive investigations in regard to diapedesis of the red corpuscles, as well as 
in regard to the escape of other elements of the body which have been introduced into 
the blood-vessels, we owe to Arnold (VircJi. Arch., 58, 62, 64 Bd.). Arnold believes 
that we must assume the presence of openings in the endothelial tube at the point of 
exit of Lhe corpuscular elements; these openings he designated as stigmata and stomata. 
Later he recognized the supposed openings to be local accumulations of the cement- 
substance between the endothelial cells. Under pathological conditions the cement- 
substance becomes softened and permits the passage of the red cells. 

§ 44. The causes of interruption of continuity of the heart=wall 
and vessel=walls are in part traitmatlc iujuries, in -part increase of intra- 
vasctdar pressure, and in part diseased condition of the heart and vessel-wall 
Increase of the blood-pressure in the capillaries and smallest veins can 
lead to rupture without the aid of vascular changes, particularly in the 
case of marked passive congestion. The heart, normal arteries, and nor- 
mal veins of large size cannot be ruptured through increase of pressure 
alone, but abnormally thin-walled or diseased areas in either the heart, 
arteries, or veins may be so ruptured. Newly formed vessels are easily 
torn. 

Diapedesis may be caused by an increase of pressure in the capillaries 



158 



DISTURBANCES OF THE CIRCULATIOX. 



aud veins, as well as by au increased lyermeahiJity of the vessel-icaJl. If the 
outflow of the veuoiis blood in a given vascular area be totally ob- 
structed, diapedesis of red cells from the capillaries and veins takes place ; 
and this is to be regarded as a result of the increased pressure in the ves- 
sels. Diapedesis as a result of changes in the vessel-wall occui-s particu- 
larly after mechanical, chemical, and thermal lesions of the vessel ; and 
it may be assumed that certam poisons produce especially marked changes 
in the vessel- walls. Further, an abnormal permeability of the vessel - 
walls is also observed when for a long period the vessels hare not been 
traversed by the blood-stream, and have suffered in their nutrition m 
consequence. 

AVhen an individual shows a special tendency to hiemorrhage, the 
condition is designated as hsemorrhagic diathesis. Two forms may l)e 
distinguished — a congenital and an acquired. 

The congenital hsemorrhagic diathesis or congenital hfemophilia, 

which, as already mentioned in §§ 16 and 17, belongs to the diseases 
which may be inherited, depends most probably upon an abnormal con- 
stitution of the vessel-walls. The composition of the blood may also be 
pathological, so that a haemorrhage once started is not arrested, as usual, 
by the coagulation of the blood. 

An acquired hsemorrhagic diathesis occurs, in the first place, in 
those diseases which are known as scurvy, morbus maculosus Werlhofii, 
purx^ura simplex, purpura (peliosis) rheumatica, purpura haemorrhagica, 
haemophilia, and melaena neonatorum, and Moller's or Barlow's disease; 
and, further, in many infections and intoxications — namely, septicaemia, 
endocarditis, anthrax, typhus fever, cholera, smallpox, plague, acute 
yellow atrophy of the liver, yellow fever, nephritis, phosphorus poison- 
ing, after snake-bites, etc. ; and, finally, also in pernicious anaemia, leu- 
kaemia, and pseudoleukaemia. In the first group of diseases named — all 
of which are characterized by haemorrhages in the skin, mucous mem- 
branes, and parenchyma of other organs and tissues (in Barlow's disease, 
which often occurs in children of from one and one-half to two years old 
in association with rickets, the haemorrhages are subperiosteal )— the cause 
has been generally sui3posed to lie in disturbances of nutrition and of the 
circulation; but recent observations make it very i^-obable that these 
affections, at least in a great part, belong to the infectious diseases. W. 
Koch is of the opinion that scurvy is an infectious disease, and that the 
different forms of puri^ura, erythema nodosum, and the haemorihages oc- 
curring in the new-born represent varieties of this infection. In the last 
few years bacteria have been repeatedly found in these conditions — 
namely, pur^^ura haemorrhagica and the haemophilia of the new-born. In 
this connection should be mentioned especially the investigations of Kolb, 
Babes, Gartner, Tizzoni, and Giovannini, who have found in these dis- 
eases certain bacilli which were pathogenic for animals, and which, when 
inoculated into the latter, produced a disease characterized by haemor- 
rhages. These diseases are also associated with other infections charac- 
terized by haemorrhages, and it may be assumed that the haemorrhages are 
in part caused by local changes of the vessel-icaJl which are due to local de- 
velopment of bacteria, and in part to the injurious influence of the toxic sub- 
stances produced by the bacteria themselves. 

The haemorrhages occurring in anaemic conditions are to be regarded 
as the result of amemic degeneration of the vessel- wall, though partly also 
as a result of circulatory disturbances. 

A number of apparently spontaneous ]i;pmorrhages are connected with 



HEMORRHAGE. 



159 



irritation or paralysis of the vasomotor nerves, arising either from the cen- 
tral nervous system or by reflex action, or through lesions of the con- 
ducting nerve -fibres. In this category belong the haemorrhage of men- 
struation, many forms of hsemorrhage from the nose, intestine, and 
urinary bladder, also haemorrhages from the conjunctiva, skin (stigmati- 
zation), from the normal kidney, mammary glands, from haemorrhoids, 
wounds, etc. Further, certain haemorrhages from the lungs following- 
severe cerebral lesions are also to be considered in this connection, 
though in a given case it is not always possible to judge with certainty, 
since disturbances of respiration, as well as the aspiration of irritating 
substances into the lungs, may likewise lead to hyperaemia and to haemor- 
rhages in the lung. Finally, in cerebral disease, particularly in disease 
of the crura cerebri, there occur haemorrhages from the stomach and in- 
testines, which are dependent upon the cerebral lesion. According to 
von Preuschen, the condition known as melaena neonatorum, which is 
characterized by the occurrence of gastric and intestinal haemorrhages 
during the first days of extra-uterine life, belongs also iu this category, 
inasmuch as during labor haemorrhages and effusions into the brain and 
its membranes not infrequently occur, as a result of which the intestinal 
haemorrhages follow. By others (Gartner) melaena neonatorum is re- 
garded as an infectious disease. 

Hcemorrhages per rhexin cease when the extravascular pressure comes 
to equal the pressure within the bleeding vessel, or when the narrowing 
of the vessel and the processes of coagulation and thrombosis close the 
rent. Hcemorrhage by diapedesis ceases through a cessation of blood-sup- 
ply to the bleeding vessel, or when the abnormal intravascular pressure 
is lowered and the vessel-wall is restored to its normal state. 



Literature. 

( Congenital Hcemophilia. ) 

Coates: North Amer. Med. and Surg. Jour., 1828. 
Dunn: Amer. Jour, of Med. Sc., 1893. 
Fischer : Zur Kenntniss der Hamophilie, Miiucben, 1889. 
Grandidier: Die Hamophilie, 1877. 

Hoffmann: Lehrb. d. Constitutionskrankheiten, Stuttgart, 1893. 

Hossli: Geschichte u. Stammbaum der Bluter von Tenna. Inaug.-Diss., Basel, 1885. 

Koch: Die Bluterkrankheit, Stuttgart, 1889. 

Legg: Treatise on Hsemophilia, London, 1872. 

Lessen: Bluterfamilie. Deut. Zeitschr. f. Chir., vii. 

Otto: iVIedical Repository, K Y., 1803. 

{Hcemorrhage due to Various Causes. ) 

Afanasiew: Mikroorganism. a. d. Gruppe d. Septikoemia htemorrhag. Cent, f . Bakt. , 
xiii.. 1893. 

Babes: Bacillen d. hamorrh. Infection. Cbl. f. Bakt., ix., 1891: Bacille produis.'les 
hemorrhagies dans le scorbut. Arch, de med. exp., v., 1893; Infect, hemorrhag. 
Ann. de I'lnst. de Path, de Bucarest, iv., 1894. 

Claisse: Purpura a pneumocoque. Arch, de med. exp., iii., 1891. 

Dennig-: Ueber septische Erkrankungen, Leipzig, 1891. 

V. Dung-ern: Hamorrhag. Sepsis bei Neugeborenen. Cbl. f. Bakt., xiv., 1893. 
Fujinami: Entsteh. d. hamorrhag. Lungeninfarkts. Virch. Arch., 152 Bd., 1898. 
Gaertner: Bakterienbefimd bei Mela?na (Bacillen). Arch. f. Gyn.. 45 Bd., 1894. 
Hamill : Haemorrhage into the Suprarenal Capsule in Still-born Children and Infants. 
Arch, of Ped., 1901. 

Harle: Die Purpura u. ihr Verhaltniss zum Skorbut. Inaug.-Diss., Heidelberg, 1897. 



160 



DISTURBA^XES OF THE CIRCULATIOX. 



Klein: Xenere Arbeitin uhw Bavlow'sclie Kranklaii. C'lil. f. allg. Path.. 1S97 (Lit.). 
Koch.: Dii' Blutrrkrankhcir ii. ilire Yaiianten. Stutiuart. l^.^O. 

Kolb: Aetiologie d. idiopath. Blutfleckenkraukheir. Arb. a. d. K. G.-A., vii., Berlin, 
1891. 

Kratter: Diagnose d. Ei>ricknng. Yierteljalirs^sclir. f. ger. ]\Ied., 1895 (Blutungen 

tinden sirli iiaiiu'iitlit li im iX'troinediasrinak'ii G(-■^vebl■l iLit. i. 
Neumann: 3Iciauua neuiiatoi'uni. Arcli. f. Kinderheilk.. xii.. 1890. 
Reimar: Retiuiris haemorrhaii-ica iu fola'e Endarteritis proliferaus. Ann. f. Aiiiren- 

beilk.. 38 Bd.. 1899. 
Runge: Die Krankheit der ersten Leben>tage. Stuttgart. 1893. 

Schoedel ii. Nauwerck: Uuters. lib. d. 31oUer-Barlow"sche Krankheit. Jena. 1900 
(Lit). 

Tavel 11. De Q,uervain: Hamorrhaa:. Bakteriilmie d. Neus-eborenen. Cent. f. Bakt., 
xii.. 1892. 

Tizzoni u. Giovannini: Entstehung d. hamorrhag. Infection. Beitr. v. Ziealer, vi, 
1889. 

Voges: Hamorrhag. Septikamie. Zeitschr. f. Hvg.. 23 Bd.. 1896. 

(XeuropafJi ic RivmorrJiages. ) 

Charcot: Leeons siir les maladies dn systeme nerveux. (Euvr. compl.. 1. 
Ebstein: Blutextravasate iu der 3Iageuschleimhaiit. Arch. f. exp. Path., ii.. 1874. 
Flatten: Limo-enaffectionen nach Kopfverletzimo-en. Eulenburo-'s Alerteljahrsschr., 
53 Bd., 1890. 

Hiitler: In den Luugen nach Verletzungen d. Geliirns auftret. Bhuungen. Oesterr. 
med. Jahrb. 1875. 

Jehn: Bbitaiistritte in d. Luugengewebe bei Hirnleiden. Cbl. f, d, med. Wiss., 1874. 

Klemperer: Xiereublntimgen b. gesunden Xieren. Dent. med. AVocli.. 1^77. 

Nau: Coutrib. a I'etude de la congestion et de I'apoplexie unilaterale dans les cas de 

ramollissement du cerveau, Paris. 1>^7. 
Nothnagel: Hirnverk^t/.iingen u. Luiigrnluimorrhagie. Cb. f. d. med. Wiss.. 1874. 
Ollivier: De raiiMpU-xic pulnionaire unilaterale dans scs rapports avec Themorrhagie 

ce]'el)rale. Aveh. gen. denit';!.. l^^To. 
Pisenti: Emorragie da causa nervosa. Lav. dell" In^tit. Anat. Patol. di Perugia. 1890. 
V, Preusclien: Verletz.uuien des Kindes al-> Ur-aelie eler AKlaeua neonatorum. Wieu, 

1894. 

V. Recklinghausen: Allg. Pathol, des Kreislaufs u. der Ernahrung. Stuttgart, 1883. 
Vulpian: Lecous sur I'appareil vasomoteur, 1875. 

g 45. The sudden closure of an arterj^ by thrombosis, or embolism, 
or by ligation, or by auy other means, leads, as has already been stated 
(§37), to a stoppage of the circulation beyond tlie point of obstruction, 
after the vessel lias more or less completely emptied itself by the con- 
traction of its vails. At the same time tlu-re is an increase ot pressure 
in the vessel from the point of obstruction back to the i^oint of divei^gence 
of the nearest arterial branch. If the branches of the artery beyond the 
point of obstruction have free arterial communication with some other 
unobstructed artery, the latter by becoming dilated may be able to sup- 
ply a sufficient amount of blood to the affected area and the circulation 
is thus restored. 

If the area of the obstructed artery has no collateral connections 
through which it may draw its blood-supply, the portion of tissue de- 
prived of blood remain.^^ an;3emic and dies, thus giving rise to an ansemic 
infarct. Pareuchymatous organs — as. for example, the spleen and the 
kidneys — present in such infarcted aix^as a cloudy, opaque, yellowish- 
white, often clay-colored appearance. The microscopical examinatiou 
shows that the tissues are dead, the nuclei no longer staining (Fig. 29, c, 
d, e, /, r/). 

Wheu the area of distribution of the obstructed vessel possesses no 
collateral anastomoses, as in the case of a terminal artery, but if. on the 
other hand, there is a scanty influx of blood from neighboring capillaries 



ANEMIC AND HEMORRHAGIC INFARCTION. 



161 



or from the veins, a hasmorrhagic infarct may be formed. The capil- 
laries of the area rendered angemic by the obstruction become gradually 
tilled once more vrith blood, which in j)art comes from the capillaries of 
the adjacent vascular area, and in part from the veins, from which the 
blood Hows in a retrograde direction. The blood flowing in from the 
adjacent capillaries is under very low pressure, which is not sufacient to 
dri\ e the blood quickly through the obstructed area into the veins. 
When the conditions of pressure become such that a retrograde current 
sets in from the veins into the capillaries, the restoration of the normal 
circulation becomes wholly impossible. 

The imperfect circulation in the obstructed area, which through proc- 
esses of coagulation in the veins (Fig. 30, c) and capillaries («) is finally 
brought to a complete standstill, leads, in case there is not a restoration 




Fig. 29.— From the edge of an anemic infarct of the kidney. (Miiller's fluid, haematoxylin, and eosin.) 
a. Normal kidney tissue r^i, normal kidney-tubules with stroma inflltrated with leucocytes; b, normal 
glomerulus ; c, necrotic tissue without nuclei, showing srrainUar coasrula in the tubules ; cl, necrotic swollen 
glomerulus with few nuclei ; e, tubules without nuclei in a stroma still containing nuclei ; /, necrotic tissue 
vrith cellular, g, with ha?morrhagic inQltration. X 50. 



of the normal flow of blood in the vascular system through a speedy ad- 
justment of pressure, sooner or later to a deg'eneration and necrosis of 
the vessel -wall, and thereby to an increased permeability of the same. 
Asa result, if the afflux of blood be continued, there occurs in the stag- 
nated area a diaj)edesis of red cells and an infiltration of the tissue with 
extra vasated blood corx)uscles, through which the obstructed ai^ea ac- 
cpiires a dark -red color and a firmer consistency ; a luemorrhag/c in farct 
is thus formed. 

Embolic hemorrhagic infarcts occur in the lungs (Fig. 30), l)ut are 
formed after the embolic obstruction of an artery only ivhen there exists a 
passive congestion of the Jungs ; while in the case of a normal pulmonary 
circulation the disturbances of circulation produced by the embolism are 
quickly compensated. In the systemic circulation extensive embolic 
haemorrhages are confined almost entirely to the region of distribution 



162 



DISTURBANCES OF THE CIRCULATION. 



of the superior mesenteric artery, whose branches, though not terminal 
arteries, possess but few anastomoses. Ancemic infarcts occur especially 
in the sjyleen, heart, Jxidneys. and retina. Around the perix^her^^ of the 
angemic area there is always more or less haemorrhage, so that the -pale 
area of the infarct is surrounded by a hcemorrliagic border or at least by 
luemorrliagic spots (Fig. 29, g). The necrotic tissue, furthermore, becomes 
infiltrated with fluid, and may therefore swell (Fig. 29, d) and show 
granular or thready coagula^ in its spaces (Fig. 29, c). In the case of 
obstruction of the cerebral arteries or those of the extremities, or the 
central artery of the retina punctate haemorrhages may also occur. 
Within the infarcted area the tissues are wholly or for the greater part 
dead, and the specific elements of the organ in particular (Fig. 29, c, d), 
die quickly. After a time an exudative inflammation arises in the 
neighborhood of anaemic and haemorrhagic infarcts, with the formation 




Fig. 30.— Edge of a fresh hgemoiThagie infarct of the lung. (Miiller's fluid, haematoxylin. and eosin.) 
a. Alveolar septa without nuclei, with capillaries filled with homogeneous, dark bluish-violet thrombus- 
masses ; Z), septa containing nuclei ; c, vein with red thrombus ; d, alveoli distended with firm blood-clots; 
f, alveoli filled with serous fluid, fibrin, and leucocytes. X 90. 

of a cellular (Fig. 29, /) or a cellular and fibrinous exudate (Fig. 30, e) ; 
and this is followed by tissue-proliferation through which the dead, 
haemorrhagic area is gradually absorbed and replaced by connective 
tissue (see Part II. of Chapter TII. ) . 

VircJio/r, Avlio was the first to cany out extensive experimental investigations 
with reference to thrombosis and embolism, leaves in his published works the question 
of the origin of embolic h^emorrhagic infarcts still open; but expresses the opinion that 
most probably the vessel-walls in the obstructed area sutfer changes by which they 
become more permeable and fragile. If a collateral circulation be afterward estab- 
lished, secondary hoemorrhage, exudation, and extravasation take place as the result of 
the changes in the vessel-wall. Colinheim, who studied the results of embolism in the 
frog's tongue directly under the microscope, demonstrated the retrograde flow of blood 
m the veins, the refilling of the capillaries, and the escape of blood by diapedesis. 
The cause of the diapedesis he believed to be essentially the disorganization of the 
vessel-wall caused by the anaemia. Liiten regarded the retrograde flow of blood from 
the veins as unessential, and referred the refining of the ana?mic area to an influx of 
blood from the capillaries of the neigli boring vascidar areas. He also regarded the 
disorganization of the vessel-walls as tmnecessary for the production of infarction, in- 
asmuch as the stagnation is sutiicieut in itself, as in the case of venous obstruction, to 
explain the diapedesis. The diapedesis is therefore increased whenever in such foci 
the blood coagulates in the efferent veins. 



HEMORRHAGIC INFARCTION: LYMPHORRHAGIA. 



163 



Von Recklinghausen cousiders the principal factor in the formation of a liacmor- 
rhagic infarct to 'be a hyaline thrombosis of the capillaries of the obstructed area. If 
blood subsequently enters from neighboring- vessels into the still pervious vessels of 
the area, it encounters resistance, becomes stagnant, and then escapes from the vessels. 
According to Klebft {Schiceizer Arch. f. Thierheilk., 28 Bd., 1886). emboli introduced into 
the circulation of animals lead to the formation of infarcts, only wlien blood rich in 
ferment is injected after the embolus, or when substances exciting coagulation are 
mixed with the obstructing plug. 

Embolic luemorrhagic infarcts of the lung occur in man, especially in passive 
congestion of the lungs; the introduction of emboli into the pulmonary arteries of 
animals with normal pulmonary circulation is not followed by infarction. The essen- 
tial cause of the escape of blood in the case of haemorrhagic infarction lies in the stag- 
nation of the blood in the affected area, and in the degeneration or death of the tissue and 
the blood-vessel walls. The latter change may be recognized with certainty through 
the disappearance of the nuclei (Fig. 30, a). Secondary thrombosis in the vessels of the 
obstructed area (Fig. 30, c) is of frequent occurrence, and increases the stagnation and 
htemorrhage, but tlirombi are not always present at tlie time of the haemorrhage, and, 
therefore, cannot be regarded as the essential factor in the production of the latter. 

According to investigations by Orih, haemorrhagic infarcts may be produced in dogs 
through the introduction of chemically irritating emboli into the pulmonary arteries. 

In the lungs, in conditions of passive congestion and inflammation, there not infre- 
quently occur extensive hsemorrhages, which, in case they are restricted to a circum- 
scribed area, closely resemble infarcts. They are usually less sharply outlined and less 
firm, so that in the majority of cases they are easily distinguished from the embolic 
infarcts. 

Literature. 

{Hcemorrliagic Infarction. ) 
Cohn: Klinik der embolischen Gefasskranklieiten, Berlin, 1860. 

Cohnheiui: Untersuch. lib. d. embol. Processe, Berlin, 1872; Allgem. Pathol., Berlin, 
1882. 

Faber: Die Embolic der Art. mesenterica sup. Deut. Arch. f. klin. Med., 1875. 
Fischer: Ueber die Embolic der Art. centralis retinsB, Leipzig, 1890. 
Grawitz: Die hamorrliag. Infarkte d. Lungen. Festschr. d. Assist, f. Virchow, Ber- 
lin, 1891. 

Kaufmann: Verschluss d. Art. mesenterica sup. durch Embolic. Yirch. Arch., 116 
Bd., 1889. 

Krebs: Hyaline Tliromben in hamorrhagischen Infarkten. Beitr. v. Ziegler, ii., 1888, 
p. 472. 

Litten: Ueber die Folgen des Verschlusses d. A. mesent. superior. Virch. Arch., 63 
Bd., 1875; Untersuchungen liber den hamorrhagischen Infarkt, Berlin, 1879. 

liukjanow: Allgem. Pathologic des Gefassystems, Leipzig, 1895. 

Mog-ling: Zur Kenntniss des hiimorrhag. Infarktes. Beitr. v. Ziegler, i., Jena, 1886. 

Obermuller : Hyaline Thrombusbildung u. hamorrhag. Lungeninfarkte. Inaug.-Diss., 
Strassburg, 1886. 

Orth: Erzeugung des hamorrhag. Infarktes. Cbl. f. allg. Path., 1897, p. 859. 
V. Recklinghausen: Handb. d. allg. Path. d. Kreislaufs u. d. Ernahrung, Stuttgart, 
1883. 

Ribbert: Niereninfarkte. Virch. Arch., 155 Bd., 1899. 

Schaffer: Ueber das sog. Hyalin in Lungeninfarkten. Fortsch. d. Med., vi., 1888. 
Virchow: Handb. d. spec. Pathol., i., 1854; Ges. Abhandl, Frankfurt, 1856. 
"Welch: Ha'morrhagic Infarction. Trans. Assn. Amer. Phys., 1887. 
"Willg-erodt : Hamorrhag. Infarkte d. Lunge. Arb. a. d. path. Inst, zu Gottingen, 
Berlin, 1893. 

Woolley : Thrombosis of the Central Vein of the Right Adrenal with Engorgement 
and Necrosis (Infarction). Jour, of Med. Research, 1902. 



VI. Lymphorrhagia. 

§ 46. Lymphorrhagia occurs when the continuity of a lymph- vessel 
is interrupted at any point and the lymph is poured out into the neigh- 
boring tissue. Since the pressure in the lymph- vessels is veiy low — that 
is, not greater than in the surrounding tissues — an outflow of lymph 



164 



DISTURBANCES OF THE CIRCULATION. 



from a lymph-vessel can occur only when the injured vessel lies on the 
external surface, or when a natural cavity is at hand into which the 
lymph can flow, or when, thi ough the same cause producing the rupture, 
an open space is formed at the same time in the tissues. So, for exam- 
ple, an escape of lymph together with the blood may take iDlace ti om 
wounds, but the outflow is stopped by very slight counteri^ressure. if, 
after the wounding of a lymphatic, the opening persists, so that there is 
a permanent outflow of lymph, escaping externally (as in ulcers) or into 
one of the body-cavities, there is formed a lymph=fistula, thi ough which 
considerable quantities of Ij^mj^h msbj be lost. Most imjiortant and also 
most dangerous is the rupture of the thoracic duct, which occurs sometimes 
as the result of traumatism, and occasionally as a result of an obsti uc- 
tion to the lymph-flow at some point in the lumen of the duct (after in- 
flammation or in the course of the growth of tumors). The lymph is 
poured out into the thoracic or abdominal cavity, giving rise to a chylous 
hydrothorax or a chylous ascites, or in very rare cases to a chyJope ricardium. 

In very rare cases it happens that the urine, as it comes fi-om the bladder, has the 
appearance of a milk-white, or a 3'ellowish, or, through the admixture of blood, a red- 
dish emulsion; and contains besides albumin a larg-e quantity of tineh'-divided fat- 
droplets. This phenomenon is kncvn as chyluria. It occurs as an endemic disease 
in certain tropical regions (Brazil, India, the Antilles, Zanzibar. Eg\vpt) where it is 
caused by a parasite, the Filaria Bancrofti, which Inhabits the l^'mph-vessels of the 
abdominal cavity and there produces its embryos {Filaria sanguinis); these, during the 
repose of the patient in a horizontal position, swarm in great numbers in the blood, 
and are also found in the ch^dous urine. The connection between the ch^duria and the 
invasion of the lymph-vessels has not yet been satisfactorily demonstrated by anatomi- 
cal investigations; but it is probable lhat the chyle-like fluid does not come from the 
blood and through the kidneys; but, as a result of the obstruction in the lymph-circu- 
lation, chyle escapes from ruptured lymphatics of the bladder and mingles with the 
urine {Scheube, Grimm). In corroboration of this view is the fact that, at autopsy, the 
abdominal lymphatics exhibit marked dilatation {Havelhurg), while the kidnej^s are but 
little changed; and further, according to an observation made by HaveUnrrg, the urine 
obtained from the ureter showed no admixture of chyle, though chyluria was present 
at the same time. 

Literature. 

(Chylous Effusions in the Body - cavities Chyluria.) 

Bargebuhr: Ascites chylosus. Deut. Arch. f. klin. Med., 51 Bd., 1893; Chylose Er- 

glisse im Pleuraraum, ib., 54 Bd., 1895 (Lit.). 
Busey: Amer. Jour, of Med. Sciences, 1889. 

Edwards : Chylous and xidipose Ascites. Ref . Handb. of Med. Sciences, 1901. 
Goetze : Die Chylurie, Jena, 1887. 

Grimm: Ueber einen Fall von Chylurie. Virch. Arch., Ill Bd., 1888. 
Henry: Case of Indigenous Parasitic Chyluria. Med. News, 1896. 
Heydecker: Chyloser Ascites. Virch. Arch., 134 Bd., 1893. 
Letulle: Epanchements chyliformes du peritoine. Rev. de med., 1884. 
Lothrop and Pratt : Amer Jour, of Med. Sciences. 1900. 
Reichenbach : Chyloser Ascites. Virch. Arch., 123 Bd., 1891. 

Scheube: Filariakrankheit. Saraml. klin. Vortr. No. 232, 1883; Parasitare Hilmo- 
chylurie. Beitr. z. path. Anat. u. z. klin. Med. ; Festschr. f. Wagner, Leipzig. 
1887. 

Senator: Chylurie. Eulenburg's Realencyklop., iv. 
Zune: Urines chyleuses et hematochyleuses, Bruxelles, 1893, 
See also § 42. 



CHAPTER V, 



Retrograde Disturbances of Nutrition and Infiltra= 
tions of the Tissues. 

!. General Considerations Concerning the Retrograde Disturbances 
of Nutrition and the Tissue=Infiltrations. 

§ 47. The retrograde disturbances of nutrition are characterized in 
general by degeneration of the affected tissue, often also by diminution in 
size and disappearance of the individual tissue- elements, the functional capac- 
ity of the tissue being, at the same time, lowered. 

The tissue=inf iltrations are characterized essentially by the deposit in 
the tissue of pathological substances which have either been formed within 
the body or introduced into it from without. The functional capacity of 
the part affected is likewise umatXlj dinfiinished. The infiltration is often 
only a restdt of preceding degenerative changes, or may itself constitide the 
chief feature of the degenercdion. 

Eetrograde disturbances of nutrition may affect the body in its fully 
developed state, or duriug its period of development and growth ; and in 
either case may lead to an abnormal smallness of the affected organ or 
tissue. In the former case the diminution in size is due to a disappear- 
ance of the individual elements of the affected tissue, and is designated 
atrophy. In the latter case, on the other hand, it is due to a defective 
development of the affected organ, as shown by a more or less rudimen- 
tary condition of its elements. If in this way an organ or a part of an 
organ wholly fails of development, so that it is totally absent or at least 
is represented only by its rudimentary anlage, the condition is designated 
agenesia or aplasia. But if the development of the affected part is of a 
certain degree, yet not reaching the normal, the condition is known as 
hypoplasia. 

The causes of agenesia and hypoplasia are partly intrinsic, and 
partly extrinsic — that is, the stunting and imperfect development of an 
organ may depend as well upon a pathological condition of its anlage, 
as upon external injurious influences which may affect the develoijing 
part. The disturbance of development may further affect either the 
whole body or only a part of the same. In the first case there results a 
dicarf ; in the second, a stimting of individual parts or organs. 

The causes of the tissue=degenerations and the associated atrophy 
are for the greater part to be found in extrinsic harmful influences to 
which the tissues are exposed during life ; but they may also depend 
upon intrinsic conditions. This latter is particularly the case when the 
tissues in old age reach their physiological limit and gradually become 
incapable of properly nourishing and preserving themselves. In many 
tissues a similar retrograde change, due to intrinsic causes, occurs earlier 
in life, as, for example, physiologically in the ovary and thymus. 

As extrinsic harmful influences which may lead to degenerations 

165 



166 



THE RETROGRADE CHANGES. 



should be cousidered all those agencies mentioned in Chapter I. Dis- 
turbances of circulation, lack of oxygen and food supply, and intoxica- 
tions play a very important role. In the majority of cases degenerations 
are localized, so that we may speak of degenerations of special tissues 
or of special organs. Not infrequently the disturbances of nutrition 
are more general, so that the entire organism suffers. Thus the picture 
of a general disease may be produced by a degenerative or atrophic con- 
dition of the blood — that is, a diminution in the number of red blood- 
cells (oligocythsemia), at times also a deficiency of haemoglobin (chloro- 
sis), so that a permanent condition of insufficient blood=supply or a 
general anaemia is produced, the nutrition of the body being corre- 
spondingly impaired. 

As the result of a diminished ingestion of food, or of disturbed me- 
tabolism, and of an increased waste of the proteids and fats of the body, 
there may result a condition of general emaciation and weakness, often 
associated with ansemia, a wasting of the entire body, which is designated 
cachexia or marasmus. If under such circumstances it appears likely 
that certain substances are formed in the body, which, when taken up 
into the blood and tissue juices, cause a contamination or alteration of 
these, the condition may be spoken of as a dyscrasia. 

Literature. 

(Disturbances of Nutrition. ) 

Charcot: Maladies des vieillards. CEuvr. compl., vii., 1890. 

Demange : 'kt. clin. et anatomo-patliol. sur la vieillesse, Paris, 1886. 

Le Gendre: Troubles et maladies de la nutrition. Traite de med., 1., Paris, 1891. 

Halliburton: Cliemische Physiologie und Pathologic, Heidelberg, 1893. 

Hoifmann : Lehrbucli der Constitutionskrankheiten, Stuttgart, 1892. 

Krehl : Pathologische Pli3^siologie, Leipzig, 1898. 

Neumeister: Lehrbucli der physiologischen Chemie, i., Jena, 1893. 

V. Noorden: Pathologic des Stoffwechsels, Berlin, 1893. 

V. Recklinghausen: Pathologic des Kreislaufs u. der Ernahrung, Stuttgart, 1883. 
Verworn: Allgemeiue Physiologie, Jena, 1897. 

11. Death of the Organism. 

§ 48. All life comes sooner or later to an end — to death. When this 
occurs at an advanced age, without preceding well-defined symptoms of 
disease, it may be regarded as a normal termination of life. This occur- 
rence may be attributed, at least in part, to the fact that the functions of 
certain organs necessary to the maintenance of life, become discontinued 
as the result of intrinsic causes ; although in most cases it is impossible 
to exclude the influence of extrinsic influences in helping to bring about 
the cessation of function of the organs in question. 

When death occurs pi'ematurely — that is, at an age earlier than the 
average age of death in man —and when preceded by symptoms of dis- 
ease, it must be regarded as a pathological phenomenon. Its occurrence 
under these circumstances is for the most part referable to demonstrable 
extrinsic influences, but at times may be dependent also upon intrinsic 
inherited causes. It is obviously impossible to draw any sharp line of 
separation between physiological and pathological death. 

The causes of premature — that is, pathological — death are to be found 
in those influences, which have been discussed in Chapters I. and II. as 
the causes of disease. 



DEATH. 



167 



An individual is to be regarded as dead when all of his functions 
have forever ceased. Death is inevitable at that instant in which one or 
more of the functions imperatively necessary to life has ceased, though 
it is not necessary that at that moment all the functions should have 
ceased. Indeed, it often happens, that after life is irretrievably lost, 
many organs are still capable of performing their function, and it is 
only after a certain time that all the organs die. The life of the organism 
passes gradually, hy ijrogressive cessation of the functions of its different or- 
gans, into the state of death. 

Cessation of the functions of the heart, lungs, and nervous system 
results in an immediate death of the entire organism. Cessation of the 
functions of the intestines, liver, or kidneys leads inevitably to death 
after a certain length of time, often measured by days. Destruction of 
the sexual glands does not endanger the life or health of the affected indi- 
vidual, and likewise man may also spare one or more of his organs of 
special sense. 

The occurrence of death is usually determined by the last recogniz- 
able efforts at respiration and by the stoppage of the heart. With the 
cessation of respiration it is impossible for any organ to remain alive 
after a certain short period. The stoppage of the heart likewise makes 
impossible any further nourishment of the tissues, in consequence of 
which the central nervons system very quickly becomes unable to con- 
tinue its functions. 

After death the body may present a variety of appearances. The 
aspect of the external visible portions is largely dej)endent upon the dis- 
tribution of the blood at the time of death. An abundant supply of 
blood in the skin gives it a blue-red color, anaemia gives it a pale color. 
Further, the preceding disease may alter the external appearance of the 
body in different ways. 

Within a certain time after death various changes occur in the tis- 
sues of the body, which in part may be regarded as the absolute signs 
of death. In the first place the temperature of the hody falls, sometimes 
rapidly, at other times slowly, until it reaches the temperature of the 
surrounding air. It must be borne in mind, however, that the temjier- 
ature at times does not begin to sink immediately after death, but first 
rises somewhat. The rate of cooling of the body depends partly upon 
the cliaracter of the body itself, and partly upon the nature of its sur- 
roundings. The tiine required may vary from one to twenty -four hours. 

The coldness of the dead hody is termed algor mortis. 

At the time of death the skin for the greater part becomes pale ; but 
after six to twelve hours, sometimes earlier, bluish-red spots appear on 
the skin over the dependent parts of the body. These are known as the 
death-spots or livores mortis (post-mortem hypostasis), and are due to the 
local accumulation of blood in the veins and capillaries of the more de- 
pendent portions. They are not found in those parts of the body sub- 
jected to the pressure of the weight of the body. Their number and size 
depend upon the amount of blood in the skin at the time of death. 
Parts which have been cyanotic during life may retain this appearance 
after death, especially the head, fingers, and toes. The color of post- 
mortem hypostasis is usually blue-red ; the intensity of the color varies ; 
in cases of poisoning with carbon monoxide it is a bright red. 

The weight of the body causes flattening of those muscular parts upon 
which it rests. 

Sooner or later there occurs a stiffening and contraction of the mus- 
11 



168 



THE RETROGRADE CHANGES. 



cles, due to the coagulation of the contractile substance (Bruecke, 
Kiihne). This is known as the cadaveric stiffening or rigor mortis. It 
usually comes on about four to twelve hours after death, but may occur 
almost immediately, or as late as twelve to twenty -four hours. It begins 
usually in the muscles of the jaw, throat, and neck, and extends from 
them to the trunk and extremities. After twenty-four to forty-eight 
hours it usually vanishes, but under certain conditions may persist for 
several days. 

Eigor mortis affects also the smooth muscle fibres ; and the contrac- 
tion of these in the skin gives rise to the so-called goose flesh of the 
cadaver. 

The decomposition of the cadaver begins with the disappearance of the 
rigor mortis. Its occurrence is shown partly by the odor of putrefaction, 
partly by changes of color in the skin and mucous membranes, and through 
changes in the consistency of the tissues. The commencement and prog- 
ress of putrefaction depend partly upon the condition of the body-nutri- 
tion and the nature of the disease preceding death, partly upon the 
conditions of the surroundings, especially the temperature, ^^'ot infre- 
quently putrefaction may occur in local dead areas of the body, even 
before death of the body as a whole. When putrefactive bacteria are 
present in the body, decomposition of the cadaver may begin immedi- 
ately after death. 

As an early sign of decomposition there is usually present a greenish 
discoloration of the skin, appearing first o^^er the abdomen. With the 
progress of putrefaction the unpleasant odor and discoloration increase ; 
and gases are formed in the intestine, later in the blood and in the tis- 
sues, which at the same time become soft and friable. 

Shortly after death the cornea becomes lustreless and cloudy, the eyeball 
loses its prominence, and dark spots appear in the sclera, which, gradually 
increasing in size, become confluent. These changes are due to evapor- 
ation and decomposition. If the eyelids are not closed, the uncovered 
portions of the eyeball show the results of drying. Whenever the skin has 
lost its epidermis the exposed tissues undergo desiccation. 

If all of the phenomena of life be reduced to a minhnnm, there may result a condi- 
tion of apparent death which may be mistaken for real death. Though post-mortem 
hypostasis, rigor mortis, and putrefaction are unmistakable evidences of death, these 
changes may not take place until some time after death, so that an interval is left dur- 
ing which it may under certain conditions be doubtful as to whether death has actually 
occurred. To ascertain the true condition under such circumstances it must be de- 
termined by appropriate examination whether the heart still beats, whether respiration 
still takes place, whether the blood still circulates, and whether the nerves and muscles 
retain their irritabilit}^ 

Conditions which are designated as apparent death occur under a variety of cir- 
cumstances, as, for example, in individuals suffering from cholera, in cases of cata- 
lepsy, hysteria, after excessive bodily exertion, violent concussion of the central ner- 
vous system, after severe hemorrhage, suspension of respiration through hanging, 
strangulation, or drowning, in certain cases of poisoning, after lightning-stroke, after 
prolonged exposure to cold, etc. The duration of this condition is usually only short, 
but may occasionally be extended over several hours or even days. 

According to the Investigations of Fuchs ("Ueber Todtenstarre," Zeitschr. f. Heil- 
kunde, 1900), ithe heart is the first muscle to show rigor mortis, this organ being affected 
at a time (in animals, after three to five hours) in which rigor mortis cannot be demon- 
strated in any of the skeletal muscles. 



NECROSIS. 



169 



III. Necrosis. 

§ 49. The condition of local death, or death of individual cells or 
groups of cells, is known as necrosis. As the result of necrosis the 
functions of the affected tissue are forever lost. 

The necrosis of a cell-group or of an entire organ is only under cer- 
tain conditions immediately associated with recognizable changes of 
structure. The slight histological changes which the cells undergo dur- 
ing their death do not always permit us to determine with certainty the 
exact moment of cessation of life ; nor does the macroscopic appearance 
of the visible portions of the body always inform us when a portion 
thereof becomes necrotic. 

Necrosis is therefore evident upon anatomical investigation only when 
certain changes in structure have occurred, either coincidently with the 
death or subsequently thereto. Necrosis is shown immediately by histo- 
logical changes only in the case of the action of a limited number of in- 
jurious agencies; in all other cases the necrosis is followed by such 
changes after a longer or shorter interval. According to the nature of 
the subsequent tissue -changes it is possible to distingLiish different varie- 
ties of necrosis. 

Histologically the necrosis of a cell is shown in the first place by the 
disintegration and disappea7xi7we of the nucleus, whereby the chromatin of 
the cell — that part taking nuclear stains — forms small clumps and gran- 
ules which at times pass out from the nucleus into the cell -protoplasm, 
where they become dissolved and disajDpear (karyorrkeocis). At other 
times the nucleus before its disappearance shows signs of sJirinJcing, and 
in this condition takes the nuclear stain more deeply than under normal 
conditions {pyknosis). In other cases the nucleus retains its form but loses 
its staining poiver with nuclear stains, and then dissolves and disappears 
(Fig. 31, c, d), so that in well-fixed and stained preparations no trace 
whatever of the nucleus can be found (karyolysis). Thus, for example, 
in an anaemic infarct of the spleen or kidney caused by arterial embolism 
the nuclei of the spleen and kidney cells are lost very soon after the 
death of the tissue (Fig. 29, c, d, f g). At the same time the affected 
area becomes strikingly pale, cloudy, yellowish-white, or cream-colored; 
so that the occurrence of the necrosis may be recognized by the naked 
eye. 

The protoplasm of the dying cells sooner or later also undergoes 
changes, which, according to the mode of death, may in some cases begin 
before the cells die, or in others may take place only after the cells are 
dead. The kind of change is dependent upon three factors : the nature 
of the cells themselves, the character of the destructive influence, and 
the amount and character of the fluids surrounding and infiltrating the 
cells. Amoeboid cells usually assume a globular form after death. Deli- 
cate and only slightly modified cell -bodies, rich in protoplasm, often 
become, before or after death, markedly granular, less frequently homo- 
geneous and lumpy. Through the taking -up of fluid the protoplasm or 
even the nucleus may become sicollen diH^ show drojys of fluid (vacuoles) ; 
and this may lead to breaks in the continuity of the protoplasm {plasmos- 
chisis). Not infrequently as a result of plasmoschisis _por^iow5 of the cell 
may be extruded or cut off by constriction. The ultimate end of all these 
changes is the disintegration of the protoplasm and the nucleus into granular 
masses, this process being often accompanied by a formation of fat. 



170 



THE RETROGRADE CHANGES. 



Cells which uormally undergo a marked transformation, as is the case 
with cells showing cornification, usually present less striking changes ; 
yet even these may swell and finally become dissolved. The morphologi- 
cal changes in dead cells are the least pronounced when the dying cells 
become more dense and dry {inspissation). In this case the cells only be- 
come smaller, j^t it is often seen that after the loss of the nucleus the 
cells become changed into lumpy masses. 

The injurious influences which may give rise to necrosis may be 
divided into five groups. The first two include those which destroy the 
tissue directly — mechanical and chemical forces. Thus, for example, 
a finger may be crushed by extrinsic violence, and a i^ortion of the skin 
may be destroyed by sulj)huric acid. A third grouj) of injurious influ= 
ences comprises those of a thermal character. The elevation of the 
temperature of a tissue to 54°-68° C. for any length of time leads to its 
death. Higher temperatures act 
more quickly. Eefrigeration to 
low temperatures likewise can be 
borne but a short time. A fourth 
group is caused by infection with 
animal or vegetable parasites. 
A fifth group is caused by a 
cessation of the supply of nour= 
ishment and oxygen to the 
tissues, and is known as anasmic 
necrosis or local asphyxia. 

By many writers there is rec- 
ognized besides these groups an 
especial one designated as neu= 
ropathic necrosis — that is, a 
necrosis resulting from a lesion 
of the central or peripheral ner- 
vous system. By some this form 
is believed to be dependent essen- 
tially upon a lesion of the troph- 
ic nerves, while by others it is 
attributed to disturbances of the 
circulation, constant pressure, and mechanical injury of angesthetic and 
paralyzed portions of the body. According to the observations thus far 
made upon man, and the experiments carried out upon animals, ex- 
ternal injuries and disturbances of the circulation play an important 
part in the production of this form of necrosis, and can never be wholly 
excluded. 

All those factors which seriously affect the cwculation within any part 
and lead to a stoppage of the blood-supply — such as thrombosis, embolism, 
closure of a vessel as a result of continued abnormal contraction, disease 
of the vessel-walls, or ligation, pressure on the tissue, inflammation, haem- 
orrhage, etc., may lead to necrosis of tissue, l^ot only a permanent 
cessation of the circulation, but also a temporary stoppage of the same 
lasting beyond a certain time, leads to the death of the affected tissue. 
Whether or not haemorrhage occurs in such cases is immaterial, as was 
stated in § 45, and influences only the appearance of the affected part. 
Scemorrhagic infarction has, therefore, precisely the same significance as 
an ancemic necrosis associated ivith hcemorrhage. 

When death follows quickly upon the action of an injurious agent, 




Fig. 31.— Necrosis of the epithelium of the urinary 
tubules in icterus gravis. (Miiller's fluid, gentian 
violet.) a, Normal convoluted tubule: b, ascending 
portion of the loop ; c, convoluted tubule with necrotic 
epithelium ; d, convoluted tubule with only a part of 
its epithelium necrotic ; e, normal stroma with blood- 
vessels. X 300. 



NECROSIS. 



171 



it is spokeu of as direct necrosis. When it occurs slowly and is pre- 
ceded by different tissue -degenerations it is designated indirect necrosis 
or necrobiosis. 

Mechanical, chemical, thermal, and infectious sources of injury, as 
well as anaemia, may act coincidently, or separately, one after the 
other. When the tissue is damaged by any one of the first- named 
group of injurious influences, the blood itself very often suffers a 
change, which leads to stasis and coagulation in the capillaries, as well 
as in the veins and arteries, and in this way the circulation may be 
arrested. 

Whether or not a given injury will cause necrosis of the tissue de- 
pends, not only upon its nature and severity, but also chiefly upon the 
condition of the tissue at the time of the injury. A tissue whose vital- 
ity has already been lowered as the result of long -continued disturbances 
of circulation, general marasmus, hydrsemia, changes in the composition 
of the blood, etc. , dies more easily than when in a normal condition. In 
severe cases of typhoid fever relatively slight pressure on the trochanters, 
elbows, sacrum or heels, etc., may suffice to bring about a gangrenous 
necrosis of the skin and subcutaneous tissues. Such forms of necrosis 
are known as marasmic necrosis or marasmic gangrene, and as decu- 
bitus or decubital necrosis. 
y The course of necrosis — that is, the tissue -changes resulting from the 
death of cells — is dependent upon the character of the affected tissue, its 
location, the manner of its death, and the cause of the necrosis. Further, 
the amount of lymph and blood in the tissue, and the opportunity afforded 
for the access of air and putrefactive organisms, also exert a very im- 
portant influence. Tissue -changes which preceded the necrosis, such as 
fatty degeneration, inflammation, hsemorrhage, etc., are also of signifi- 
cance in determining the character of the necrosis. 

As the result of the necrosis of a certain tissue=area, there always 
develops 2i\\infiammation of greater or less intensity in the surrounding tissues 
(Fig. 29, / and Fig. 30, e). This reactive inflammation is most marked 
when the necrotic area becomes gangrenous. Through the formation of 
an inflammatory zone the necrotic area becomes marked off from the 
surrounding tissue, and is isolated or sequestrated; this process is spoken 
of as a sequestrati7ig or limiting inflammation, and the dead area thus shut 
off is called a sequestrum. A more detailed description of these inflam- 
matory processes will be found in Chapter VII. 

Excluding the more especial complications of necrosis, such as the 
development of specific irritating substances, five chief sequelae of ne- 
crosis may be distinguished: 1. The dead tissue may be removed by 
absorption, or may be cast off from the surface, and its place taken by nor- 
mal tissue {regeneration). 2. The dead tissue is similarly removed, but 
instead of the normal tissue being restored, the defect is filled wholly or 
in part by the formation of connective tissue, the so-called cicatricial 
tissue. 3. The necrotic tissue is cast off or liquefied (as in the formation 
of a gastric ulcer through the digestion of the dead part), the defect is 
not filled in, and there remains an ulcer. 4. The necrotic tissue is partly 
absorbed, but a portion remains as a sequestrated necrotic mass which 
not infrequently later becomes calcified and surrounded by a connective-tis- 
sue capsule. 5. The area becomes encapsulated by connective tissue, the 
dead tissue becomes absorbed or liquefied, and the space becomes filled 
with fluid, forming a cyst. This sequela of necrosis occurs most fre- 
quently in the brain. 



172 



THE RETROGRADE CHANGES. 



The time required to kill tissue by the sliutting-off of the circulation varies with 
the different tissues. Ganglion-cells, kidney epithelium, and liver-cells die in two 
hours, while skin, bone, and connective tissue may live for twelve hours or longer. 
Epidermis under certain conditions may remain alive for a number of days, and still 
retain its power of proliferation (see Transplantation). 

The cause of the above-mentioned nuclear changes and of the disappearance of the 
nucleus is to be found in the infiltration of tlie necrotic tissue with lymph. These 
changes do not occur in those tissues to which, after necrosis, the lymph no longer 
obtains access. In putrefaction the nuclei disintegrate and disappear very rapidly. 
According to Fr. Kraus, tissue preserved under aseptic precautions, and protected from 
bacteria in moist chambers at the body-temperature, also loses its nuclei. Liver-tissue 
{Ooldmann) shows this change most rapidly and completely, the tissues of the spleen 
and kidney more slowly and less completel}^ so that all nuclei may not have disap- 
peared after eight to fourteen days. The disappearance of the nucleus occurs only in 
the presence of a relatively abundant supply of fluid {Goldmann), and may be pre- 
vented by desiccation of the tissue. 

§ 50. According to the various conditions in which the tissues may 
be found after they have died, four chief forms of necrosis maybe distin- 
guished : coagulation-necrosis, caseation, liquefaction-necrosis, and gangrene. 

Coaguiation=necrosis (Weigert, Cohnheim) is characterized by the 
occurrence of coagulation, either extracellular, in the fluids about the 

cells; or intracellular, in the latter 
case leading to peculiar changes with- 
in the cells. 

As coagulation-necrosis with extra- 
cellular coagulation may in the first 
place be regarded both the intravas- 
cular (Figs. 13-16) and the extr avas- 
cular (Fig. 30, d) coagulation of the 
Mood, inasmuch as this phenomenon 
may be regarded as the death of the 
blood; and in fact a destruction of 
cells does occur. Further, there may 
be considered as belonging to this 
class the various forms of coagulation 
which occur in inflammations, partly 
on the surface and partly in the in- 
terior of the tissues (see Chapter YII. ) ; and which are characterized by 
the formation, in some cases, of stringy fibrin (Fig. 32), in other cases 
by the formation of granular or hyaline masses of coagula. 

Intracellular coagidation occurs when dead cells or cell -products are 
infiltrated with a fibrinogen -containing lymph. The cells lose their nu- 
clei, present either a granular (Fig. 29, c, d, e, and Fig. 31, c, d) or a 
hyaline lumpy appearance. They remain in this condition for a certain 
time and then break down into granules and become dissolved. 

This phenomenon is most frequently observed in aniemic, toxic, and 
thermal tissue-necroses, as for example, in anaemic infarcts of the kidney 
(Fig. 29) and of the spleen, also in many inflammations which are asso- 
ciated with marked infiltration of the tissues (Fig. 32) due to exudation 
from the blood-vessels. In the necrosis of striped muscle, which is of 
very frequent occurrence in typhoid fever, the contractile substance 
acquires a hyaline waxy appearance and breaks up into hyaline lumps 
(Fig. 33, l). 

The necrotic tissue of ansemic infarcts looks pale yellowish-white, or 
cream -colored. Muscles containing many dead fibres in a state of hya- 
line coagulation are pale red, and of a dull lustre, resembling fish-flesh. 




Fig. 32.— Coagulation-necrosis in the interior 
of a greatly swollen mesenteric lymph-gland, 
from a case of typhoid fever. (Alcohol, fibrin 
stain.) Network of fibrin between the necrotic 
cells. X 300. 



COAGULATION-NECROSIS : CASEATION. 



173 




■Hyaline necrosis or waxy 
degeneration of muscle, from a case of 
typhoid fever, a. Normal muscle-flbre ; 
h, degenerated fibres, which have broken 
up into hyaline lumps ; c, cells lying with- 
in the sarcolemma ; d, connective tissue 
infiltrated with cells. X 350. 



Inflamed tissues undergoing coagulation necrosis are likewise cloudy, 
opaque, and grayish -white ; but the color may undergo marked changes 
through the admixture of blood or the 
imbibition of bile, as in the intestine, for 
exami)le. 

The structure of a tissue which is the 
seat of a coagulation -necrosis, may still 
be clearly recognized if only the more del- 
icate parts have been destroyed. When 
all pai'ts have been changed, the entire 
tissue may be converted into a structure- 
less, hyaline, or granular mass, containing 
no nuclei or but few. This change takes 
place very often in the necrosis of in- 
flamed tissues which are infiltrated with 
exudate. Through the proper treatment 
of preparations there may be frequently 
demonstrated in these necrotic areas an 
intercellular stringy fibrin; this is seen 
occasionally in anaemic infarcts, but more 
often in inflammatory tissue - necroses 
(Fig. 32). 

Caseation is a form of necrosis closely 
related to coagulation-necrosis, and is 
characterized by either a hard or a soft 

cheesy appearance of the necrotic area. In the first case the dead tissue 
is like firm, yellowish-white, hard cheese, or similar to raw potato ; in 
the second case it is white, soft, sometimes dry, sometimes moist, and 
not infrequently resembling thick cream. 

Typical caseation occurs most frequently in tubercles and represents 
the characteristic end of the retrogressive changes in this condition. It 
also occurs in syphilitic granulomata and in very cellular tumors ; in- 
flammatory exudates may also become 
changed into cheesy masses. 

The process of caseation of cellular 
tissues, which is a characteristic of tu- 
berculous granulations, takes place grad- 
ually, and is therefore to be regarded as 
a form of necrobiosis. The cells are 
changed successively into non-nucleated, 
homogeneous, lumpy masses, which later 
disintegrate and break up into a gran- 
ular mass (Fig. 34, a^, a). At the same 
time with these changes there often ap- 
pears between the cells a hyaline sub- 
stance, sometimes forming a framework 
around the cells or at other times more 
lumpy or granular, and fibrin -like — the 
so-called '^fibrinoid substance.'^ Typical 
fibriUated fibrin (Fig. 35, a) staining deep 
blue with Weigert's fibrin stain is often also present. It may therefore 
be assumed that both substances represent coagulation-products of a 
fluid which has escaped from the blood-vessels. 

Througli progressive cleavage and disintegration of the dead cells, 




Fig. 3J:. —Tissue from a partly caseated 
tuberculous focus, containing bacilli. (Al- 
cohol, fuohsin, aniline blue.) a. Granular; 
a,, lumpy masses of cheesy material; 
flbrocellular tissue ; c, partly necrotic giant- 
cell containing tubercle bacilli ; ci, bacilli 
in the cellular tissue ; e, bacilli in necrotic 
tissue; /, bacilli enclosed within cells. 
X 200. 



174 



THE RETROGRADE CHANGES. 



the fibrinoid substance, and the fibrin, the dead tissue is ultimately 
changed into a finely granular mass, in which no traces of the original 
structure can be perceived. 

The cheesy metamorphosis of the fibrino-cellular exudate, which is 
found especially in the ah eoli of the lungs in the neighborhood of tuber- 
cles, is brought about similarly by the disappearance of the nuclei, and 
the disintegration of the cells and fibrin into a non-nucleated granular 
mass. 

The granules of the soft cheesy masses in tuberculous and non-tuber- 
culous foci are chiefly albumin granules, more rarely fat-droplets. The 
ultimate fate of such masses may be partly liquefaction and jyultaceous 
softening, partly absorption, and x)artly desiccation and calcification. 

Col liquation or liquefaction=necrosis is characterized especially by 
the fact that the necrotic parts become dissolved in the fluids j^^csent in the 




Fig. 35.— Fibrin-containing tubercle from the lung. (Alcobol, haeuiatoxylin, Qbrin stain.) a. Fibrin; 
b, giant-cell ; c. cellular portion of tbe tubercle, x 3UU. 

tissues. The dissolution may be accomplished by swelling and liquefac- 
tion, as well as by a breaking up of the tissue -elements, or through a 
combination of these processes. Thus, for example, in burns of the sec- 
ond degree the cells of the epidermis, which have been killed by the 
heat, with the exception of the horny layer, become dissolved in the fluid 
exuding from the papillae (Fig. 36, d, f). In the case of an semi c infarcts 
of the brain the necrotic brain -substance undergoes softening with tlie 
formation of drops and granules, and becomes converted into a ]nilky, 
pultaceous mass in which the products of the destruction of the brain- 
tissue disintegrate into smaller and smaller particles, which, either free 
or enclosed within cells, become absorbed or completely dissolved. In 
suppurative processes of the tissues, which occur very frequently in 
purulent inflammations, the so-called pus-corpuscles become swollen, or 
disintegrate, and finally are destroyed ; while the ground-substance — as, 
for example, the connective-tissue fibres — gradually becomes dissolved. 



LIQUEFACTION : GANGRENE. 



175 



l^ecrosed areas in the mucosa of the stomach become dissolved through 
the digestive action of the gastric juices. 

Coagulation and liquefaction may not infrequently follow or precede 
each another. For example, the products of coagulation in an inflamed 
area may again become dissolved. In gangrenous blebs produced by the 
dissolution of epithelial cells, there may occur a coagulation, the prod- 
ucts of which are later again dissolved. Necrotic foci arising in the 
course of inflammations or in granulomata very often at a later stage 
become liquefied. 

The changes described above as occurring in dead or dying tissues are not the only 
ones which take place during tissue-destruction. They are only the chief types which 
occur in the course of a relatively rapid necrosis. Many of the tissue-degenerations 
described in the following paragraphs also lead, not infrequently, to ultimate death 
of the tissue, and consequently they must be regarded as belonging to the processes 
classed as tissue-necrobiosis. Granular degeneration, fatty degeneration, mucous degen- 




FiG. 36.— Blister of cat's paw. caused by hot sealiner-wax. (Alcohol, carmine.) a. Horny layer of the 
epidermis: &, rete Malpighii ; c, normal papilla; d, swollen epithelial cells whose nuclei are in part visible, 
and in part have disappeared ; e, epithelial cells l.vin^? between the papillte, the upper ones swollen and 
elongated, the lower ones preserved ; f, total liquefaction of the epithelium ; g, swollen cells of the inter- 
papillary cell-masses, which have lost their nuclei; h, a similar cell-mass which has been completely 
destroyed, and raised from the basement-membrane, by the coagulated subepithelial exudate k ; i, flattened 
papillary body infiltrated with cells. X 150. 

eration, and hydropic degeneration often end in the destruction of cells ; and the same 
result may be reached in the case of hyaline and amyloid degeneration of the connective- 
tissue, in that not only the ground- substance of the tissue is permanently altered, but 
the cells of the affected tissue also die. 

According to the investigations of Schmaus and Albrecht, kidney epithelium soon 
becomes invisible in water, salt solutions, and diluted alkalies, in that the cells become 
swollen or dissolve. Epithelial cells which have become granular through anaemic 
necrosis retain their granular structure in the solutions named. This may be taken 
as a proof that coagulation has occurred with the formation of firm bodies, not soluble 
in dilute acids, alkalies, and neutral salts, out of elements occurring originally in the 
cells in a fluid state. 

§ 51. Under the name of gangrene may be classed those forms of 
necrosis in which the tissue, partly through exposure to the air, partly 
through the agency of bacteria, suffers changes which are similar in ap- 
pearance to those occurring in burned tissues. If necrotic tissue through 
exposure to the air loses its water by evaporation and becomes dry, the 



176 



THE RETROGRADE CHANGES. 



condition is designated dry gangrene {gangrwna sicca) or mummifica= 
tion. When the dead part remains moist, the terms moist gangrene 
{gangrcena liumida) or sphacelus may be applied. If through the agency 
of bacteria there occurs ix, foul- smelling putrefaction, the condition is known 
as a putrid gangrene (gangrcena foetida). Development of gas-bubbles 
as a result of the putrefactive changes leads to emphysematous gan= 
grene (gangrcena emphysemcttosa). 

Moist gangrene and putrid gangrene are in general identical, since 
bacteria can develop only in moist tissues. ^Nevertheless a dry gangrene 
is not infrequently a putrid gangrene, since bacteria may develop in the 
tissue before drying takes place. Dry gangrene may also develop from 
a moist gangrene, or through the absorption of water become changed 
into the latter. 

When the dead tissue, in either mummification or moist gangrene, 
contains a large amount of blood, it appears black, dark brown, or 
greenish-black in color, and is then called black gangrene. If, on the 
other hand, the dead tissues are ansemic, the condition is sometimes 
spoken of as white gangrene, although there is more or less discolor- 
ation of the dead part, so that the expression is often inappropriate. 

In the case of gangrene of superficial parts of the body, there may be 
distinguished, according to the temperature of the dead part, a cold and 




Fig. 37.— Dry gangrene of the toas, due to narrowing and closure of the arteries through arteriosclerosis. 

a um^m or hot gangrene, the latter designation being used when the gan- 
grenous area is kept warm by the blood flowing through the neighboring 
tissues. 

Gangrene may be caused by external injuries, heat, cold, corrosi^ es, 
crushing, pressure, infection, etc. , as well as by disturbances of the cir- 
culation. 

Gangrene due to disturbance or arrest of the circulation occurs not 
infrequently in old people (senile gangrene), involving the extremities, 
particularly the toes, feet, and legs. It is usually of the dry variety, 
and is dependent upon general disturbances of the circulation and nar- 
rowing of the arteries of the extremities through thickening of the 
arterial wall (Fig. 37). The dying parts appear bluish -black from the 
damming-back of the blood. General disturbances of the circulation, 
as in heart-disease and embolism of the arteries may cause similar 
changes. 

Gangrene from cold affects chiefly the tips of the extremities, nose, 
and ears, and is characterized by changes similar to those described above. 

Gangrene from heat is confined to the area directly affected by the 
heat. 



GANGRENE. 



Pressure=gangrene or decubitus (bedsore) occurs in marasmic indi- 
viduals, most frequently upon the sacrum and the heels, both of which 
regions are exposed to pressure when the individual lies upon his back. 
The bedsore begins with the formation of bluish-red spots, within whose 
area the tissue dies, and through the agency of bacteria undergoes de- 
composition and finally disintegrates. The gangrenous area may be of 
large extent, especially when over the sacrum ; the bone may be laid bare 
over a large area through the destruction of the overlying soft parts. 

Toxic gangrene occurs chiefly in ergot poisoning as a result of the 
contraction of the small vessels and formation of thrombi. The tips of 
the extremities are usually aifected. 

Infectious gangrene occurs particularly in different infections of the 
skin and subcutaneous tissue, and may be associated with gas-formation. 
In the form known as foudroyant gangrene different varieties of bacteria 
have been found ; the bacillus of malignant oedema, an anaerobic bacil- 
lus (Welch, E. Frankel, Hitschmann and Lindenthal), proteus (Hauser), 
and bacterium coli. Infections associated with putrid gangrene may 
occur in the internal organs, but affect chiefly the lungs and intestines. 

A so-called neuropathic gangrene occurs when a tissue affected with 
either sensory or motor paralysis is wounded or subjected to continued 
pressure. It is dependent partly upon circulatory disturbances and 
partly upon infection. Gangrene resulting from the withdrawal of the 
influence of trophic nerves has not yet been demonstrated. Symmet= 
rical gangrene, which affects corresponding parts of the extremities 
and has been regarded by many as a neuropathic disease, is dependent 
upon changes in the blood-vessels ; likewise, the perforating ulcer of the 
foot {mal perforant du pied), which begins as a callosity following me- 
chanical influences, and is characterized by an accompanying gangrene 
which rapidly penetrates into the deeper tissues, is dependent upon the 
closure of an artery of the foot. 

In moist gangrene the tissues break down with a varying degree of 
rapidity, the fasciae resisting for the longest time. As crystalline prod- 
ucts of the chemical changes there may be found needles of fat and 
tyrosin, spherules of leucin, coffin-lid crystals of triple phosphate, and 
crystals of haimatoidin. If the gangrene comes to a standstill, the gan- 
grenous tissue becomes sequestrated through the formation of a zone 
of demarcation — that is, becomes separated from the living tissue, and 
under favorable conditions may be thrown off from the body. In the 
case of necrotic portions of bone a very long time is required for seques- 
tration. Extension of gangrene (through infection or continued circu- 
latory disturbance) leads sooner or later to death, especially if toxic sub- 
stances or bacteria are taken up into the blood or lymph. 



Literature. 

(Necrosis and Gangrene.) 

Albrecht: Neue Fragestellung z. Pathol, d. Zelle. iVIiinch. med. Woch., 1899. 
Arnheim: Coagulationsnekrose d. Kernscliwund. Yirch. Arch., 120 Bd., 1890. 
Balser: Ueber Fettnekrose. Virch. Arch., 90 Bd., 18.^2. 
Chiari: Ueber die sog. Fettnekrose. Prager med. Woch., 1893. 
Condorelli: Istio-patologia del nucleo nelle contusioni, Catania, 1891. 
Dejerine et Leloir: Alter, nerv. dans cert, cas de gangrene. Arch, de phys., 1881. 
Demme: Ueber die Veranderungen der Gewebe bei Brand, Frankfurt, 1857. 
Ellis: (X-Ray Necrosis) Lit. Amer. Jour, of Med. Sc., 1903. 



178 



THE RETROGRADE CHANGES. 



Falta: Gangraena senilis. Zeitsclir. f. Heilk., xx., 1809. 

Flexner: Fat Necrosis. Jour, of Exp. Med., 1897; Focal Necrosis. Johns Hopkins 

Hosp. Rep., 1897. 
Frangois : Essai sur les gangrenes spontanees, Paris, 1832. 

Frankel: Ueber die Gasphlegmone, Hamburg, 1898; and Miinch. med. Woch., 1899. 
Goldscliniid.t • Gangrene symetrique (endarterite obliterante). Revue demed., vii., 
1887. 

Goldmann: Veranderungen aseptisch aufbewahrter Gewebsstlicke. Fortschr. d. 

Med., vi., 1888; Reiskorperclieuhaltiges Hygrom der Sehnenscheiden. Beitr, v. 

Ziegler, vii., 1890. 
Hag'a:"Spontane Gangran. Virch. Arch., 152 Bd., 1898. 

Hartmann: Exp. Uuters. iiber Ghromsiturenephritis. Inaug.-Diss. , Freiburg, 1891. 
Hitschmann u. Lindenthal: Gangrene foudroyante. Sitzb. d. Ak. d. Wiss., V/ien, 
1899. 

Hoch.enegg' : Ueber symmetrische Gangran u. locale Asphyxie, Wien, 1886. 

Israel: Anam. Nekrose d. Nierenepithelien. Virch. Arch., 123 Bd., 1891; Biolog. 

Studien, lb., 141 Bd., 1895; 147 Bd., 1897; Tod d. Zelle. Berl. klin. Woch., 

1897. 

Kaufmann: Die Sublimatintoxication, Breslau, 1888. Virch. Arch., 117 Bd., 1889. 
Kraus: Im abgestorb. Gewebe auftretende Veranderungen. Arch. f. exp. Path., xxii., 
1886. 

Langerhans : Ueber multiple Fettgewebsnekrose. Virch. Arch., 122 Bd., 1891. 
Le Count: Focal Necrosis. Jour, of Exp. Med., 1897. 

Lesser: Anat. Veranderungen d. Verdauungskanales durch Aetzgifte. Virch. Arch., 
83 Bd., 1880. 

Levai: Mai perforant du pied. Zeit. f. Chir., 49 Bd., 1899. 

Mallory: Focal Necrosis. Jour, of Exp. Med., 1898; Necroses of the Liver. Jour. 

of Med. Research, 1901. 
Manz: Ueber die Bildung der Reiskorperchen. Inaug.-Diss., Freiburg, 1892. 
Neuberger: Wirkung des Sublimates auf die Nieren. Beitr. v. Ziegler, vi., 1889. 
Obolonsky u. Ziegler: Wirkung d. Phosphors auf Leber u. Nieren. Beitr. v. Ziegler, 

ii., 1887. 

Oertel : Die Pathogenese der epidemischen Diphtheric, Leipzig, 1887. 
Peiper: Eiterige Schmelzung der Gewebe. Virch. Arch.. 118 Bd., 1889. 
Pfitzner: Zur pathologischen Anatomic des Zellkerns. Virch. Arch., 103 Bd., 1886. 
Rath: Bakteriologie der Gangran. Cbl. f. Bakt., xxv., 1899. 

Raynaud: De I'asphyxie locale et de la gangrene symetrique des extreraites, Paris, 
1862. 

Reed: Focal Necrosis. Amer. Jour, of Med. Sc., 1895. 

Rischpler: Histol. Veranderungen nach der Erfrierung. Beitr. v. Ziegler, xxviii., 
1900. 

Schmaus: Zelltod. Ergebn. d. allg. Path., iii., Wiesbaden, 1897. 

Sclimaus u. Albreclit: Ueber Karyorrhexis. Virch. Arch., 138 Bd., 1895 (Lit.); Die 
kitsiiie Nekrose, ib., 144 Bd., Supplh., 1896; Coagulationsnekrose. Deut. med. 
Woc4i., 1899. 

Seitz: Blutung, Entzilndung u. brandiges Absterben des Pankreas, Berlin, 1892. 
Sternberg: Endarteritis u. spontane Gangran. Virch. Arch., 161 Bd., 1900. 
Stroebe: Cellulare Vorgange u. Erscheinungen in Geschwiilsten. Beitr. v. Ziegler, 
x., 1891. 

Tesdorpf: Symmetrische Gangran. Arch. f. Ps3'ch., 33 Bd., 1900. 
Verworn: Allgeni. Phj-siologie, Jena, 1897; Der kornige Zerfali. Pfliig. Arch., 63 
Bd., 1896. 

Weigert: Pathologische Gerinnungsvorgange. Virch. Arch., 79 Bd. , Coagulations- 
nekrose mit besonderer Beriicksichtigung der Hj-alinbildung und der Umpragung 
geronnener Massen. Deut. med. Woch., 1885; Weisse Thromben. Fortschr. d. 
Med., v., 1887; Coagulationsnekrose oder Inspissation. Cbl. f. allg. Path., ii., 1^91. 

Weiss: Venenspasmus. Wien. med. Presse, 1882; Sjanmetr. Gangran. Wien. med. 
Klin., 1882. 

Wells : Experimental Fat Necrosis. Jour, of Med. Research, 1903. 

IV. Hypoplasia, Agenesia, and Atrophy. 

§ 52. Hypoplasia, or the defective development of aiilage, may affect 
either the hodj as a whole, or only single organs or parts of organs, and 
ma^y occur either during the period of iutra-nterine development or later 
during the period of post-embryonal development. 



HYPOPLASIA. 



179 



When either the entire skeleton or at least the greater part of it is 
under-developed, and especially if the bones do not attain their normal 
length, the affected individual is abnormally low in stature, and is called 
a dwarf (Figs. 38 and 39). The individual parts may be fairly well pro- 
portioned (Fig. 38), or they may be unsymmetrically developed (Fig. 





FIG. 38. 

Fig. 38.— Skeleton of a female cretin, thirty-one years of age, 118 cm. in height, with klinocephalic 
skull. The cartilage sutures of the diaphyses of the long bones and pelvic bones still show ; as does also the 
frontal suture. The individual parts of the skeleton are, on the whole, in the proper proportion, the upper 
extremities alone being relatively short. 

Fig. 39.— Skeleton of a female dwarf of flfty-eight years of age, 117 cm. in height, with very short 
extremities, and Jong trunk. The cartilage sutures are still present ; the articular ends of the bones are 
thick. 

39). For example, the trunk may be of normal size, while the extrem- 
ities are abnormally short (Fig. 39) ; or both the trunk and the extrem- 
ities may be abnormally small, while the head is of normal size, and 
consequently appears relatively too large for the small body. When the 
lack of development affects individual parts of the skeleton exclusively, 
or if it is more marked in certain parts than elsewhere, there results a 
stunting of individual portions of the body. 

For example, defective development of the cranium gives rise to 



180 



THE RETROGRADE CHANGES. 



microcepJialus 
developmeut 




(Fig. 4:0) iiud viic)'e7ice2)hali(s (Fig. 41); through defective 
of the liuiiierns or of the bones of the hand there 

results a shortening of the upper 
- arm or of the hand ; and through 

liypoplasia of the lateral masses 
, of the sacrum the transverse di- 

^ ameter of the pelvis becomes dim- 
inished. 

Of the individual organs the 
.^entral nervous system (Figs. 41 




Fig. 40.— Head of Helene Becker liiiicruceplialic), 
at age of Ave years. (From a photograph taken by 
A. Ecker, in 1868.) 



Fig. 41.— Brain of Helene Becker (micro- 
cephalic) who died at the age of eight years. 
(After von Bischoff.) This brain we"ighed 
219 gm. (instead of 1,377 gm., according to 
Vlerordt). 



and 42), and the genito-urinary tract in particular suffer very frequently 
a stunting of development, although the intestines, heart, lungs, liver, 




Fig. 42.— Hypoplasia and microgyria of the left cerebral hemisphere, from a deaf-mute, a, Right 
hemisphere ; left hemisphere ; c, occipital lobe presenting a condition of microgyria ; t?, membranous 
cyst in the region of the parietal lobe. (Seen from above, after removal of the cerebellum. Two-thirds 
natural size.) 



HYPOPLASIA: AGENESIA. 



181 



etc., do not escape similar disturbances of growth. For example, the 
entire brain (Fig. 41), or only one of the hemispheres, or a part of the 
latter (Fig. 42, c, d) may fail of complete development. The intestine 






Fig. 43. 



-Hypoplasia of the uterus with well-developed ovaries, but without ripe follicles, 
twenty-eight years of age. 



From a cretin. 



may in part be represented by a thin canal incapable of functionating 
(Fig. 44, d), or even by a solid cord (Fig. 44, e). The uterus not infre- 
quently remains in an undeveloped state (infantile) (Fig. 43), and occa- 
sionally at the time of puberty the ovary (Fig. 45, e), or the entire inter- 
nal generative apparatus, and at times also the external organs of the 
female may remain in the undeveloped state of the young child. A 
more or less marked hypoplasia of the kidney is not rare. In the de- 
velopment of the respiratory tract the alveoli of a portion of the lung 
may wholly fail to develop, so 
that a part of a lobe or even an en- 
tire lobe may consist only of con- 
nective tissue and dilated bronchi. 

The above-mentioned exam- 
ples of hypoplasia, to which many 
others might be added, arise part- 
ly through intrinsic causes in- 
herent in the germ, and are there- 
fore inheritable; and partly 
through the action of extrinsic 
injurious influences upon normal 
anlage during the course of de- 
velopment. For example, the 
growth of the bones may be influ- 
enced and retarded by disease of 
the thyroid gland or through in- 
sufficient nutrition (rachitis), dis- 
use, and inflammation. Total 

failure of portions of the body or of single organs to develop is known 
as agenesia. This condition is dependent either upon the non-forma- 
tion of the anlage, or upon the destruction of the latter after they have 
begun to develop. (See Chapter on Malformations. ) 




Fig. 44. 



new-born child. 



Hypoplasia of the small intestine of the 
a. Greatly dilated portion ; c, d, e, 
portion showing great narrowing and stunting; /, 
normally developed portion. (Five-sevenths natural 
size.) 



1Sl> 



THE RETROGRADE CHANGES. 



The tissue composing hypoplastic organs or parts of organs, though 
of less bulk than normal, may jDresent no abnormalities of structure. In 
other cases there mny be associated with the smallness of size a disturb- 
ance of internal organization, so that often the more highly si^ecialized 
elements of the organ fail of development, the hypoxjlasia being at the same 
time associated with an agenesia of individual parts. Thus, for example, in 
hypoplasia of the ovary (Fig. 45, e) the development of the ova and the 
ripening of the follicles may fail in part; in hyj)oj)lasia of the brain 
there may occur at the same time a defective development of the gan- 



FiG. 45.— Cross sections of ovaries at different periods of life. (Heematoxylin and eosin.) a, ?>, c, c7, 
Normal ovaries; a, girl of Qve yeai-s ; t». twenty-three years; c, twenty-nine years; and c7, twenty-one 
years ; e, hypoplastic ovary of girl of twentj'-seven years ; /, g, senile ovaries from women of eighty and 
eighty-three years of age. (Natural size.) 



giion-cells and nerve-fibres, and at times i^ortions of the brain may con- 
sist only of membranous masses (Fig. 42, d) in which no ganglion -cells 
are present. In hypoxDlasia of the lung there may be under certain con- 
ditions a complete failure of development of the alveoli, so that the 
lung-tissue consists merely of a very vascular connective tissue through- 
out which lie the bronchi, the latter in the course of time usually be- 
coming dilated. 



Fdrster: Die Missbilduugen des Menschen, Jena, 1865. 

Hertz: Ueber Hemiatropliia facialis progressiva. Arch. f. Kinderheil. , vii., 1887. 
Hektoen: Anatomical Study of a Short-limbed Dwarf. Amer. Jour, of Med. Sc., 1903. 
Mehnert: Die individuelle Variation d. Embryo. Morph. Arb. v. Schwalbe, v., 1896. 
Paltauf, A. : Ueber den Zwergwuchs. AYien, 1891. 
Rahlmami: Mikrophthalmus u. Hemimikrosoma, Stuttgart, 1897. 
Vierordt : Anatomische, phj'siologische u. physikalische Daten u. Tabellen, Jena, 1888. 
See also Chapter IX. 

§ 53. Atrophy is a diminution in the size of an organ due either to a 
diminution in size or disappearance of its individual elements. It may 
occur at any x^eriod of life, and is a very common result of many path- 
ological i)rocesses. Within certain limits it may be regarded as a physi- 
ological phenomenon, in that in old age there constantly occurs a certain 
degree of retrograde change in all the organs, associated with a diminu- 
tion in their size. Certain organs undergo such an atrophy with partial 
or total loss of their functional power, even before old age, as, for exam- 
ple, the thymus, which atrophies completely even before the end of the 
period of growth ; and the ovary (Fig. 45, /, g), a part of whose ova are 
discharged during the period of sexual activity, the remainder being 




Literature. 



(ITypopflasia and Agenesia.) 



ATROPHY 



183 



destroyed. lu old age the lympliadeiioid tissues, the muscles and bones, 
ill particular, suffer atrophy, though the tissue-changes of senility vary 
greatly in different individuals, so that often other tissues, the glandular 
organs or the brain, show the most marked atrophy. 

The atrophy of an organ is characterized chiefly by its diminution in 
size. In atrophic conditions of the muscles (Fig. 46) the affected por- 
tions of the body become smaller, and in extreme cases the extremities 
appear as if consisting only of skin and bones. When the atrophy of an 
organ is uniform throughout, its normal shape may be preserved; but if 
the atrophy progresses more rapidly in certain parts than in others, the 
surface of the organ may show local de- 
pressions (Fig. 48) and cicatricial con- 
tractions (Fig. 51), so that the organ, for 
example, the liver or kidney, may present 
a knobbed or granular appearance. When 
tissues which are undergoing atrophy are 
prevented from contracting, as in the case 
of the bones and lungs, the external form 
is preserved. In the case of bone, the 
medullary spaces and the Haversian canals 
become enlarged, and a condition results 
which is known as excentric atrophy or 
osteoporosis (Fig. 47). In the lungs the 
alveoli become confluent into large air- 
spaces as the result of the disappearance 
of the intervening walls. 

In atrophy of the glands and muscles 
there occurs frequently a change of color, 
though this is of secondary importance. 
Either the normal pigmentation of the 
affected organ is brought out more dis- 
tinctly by its atrophy, or associated with 
the atrophy there is a deposit of pigment 
(brown or pigment atrophy), or finally the 
change of color may be dependent upon 
the changed blood-content of the atrophic 
tissue. 

The diminution in size of atrophic organs 
is the result of a diminution in size and dis- 
appearance of the histological elements com- 
posing them. In the majority of the or- 
gans, particularly in the glands, muscles, 
and bones, the specific cells which perform 
the especial function of the affected or- 
gan, are affected in atrophy to a far 
greater degree than the supporting connective-tissue framework. Indeed, 
it may be frequently observed that the connective -tissue elements may 
be wholly preserved, or even increased in number, while the more high- 
ly specialized elements have disappeared. Thus, for example, in 
atrophic muscle (Fig. 49) the contractile substance within the sarco- 
lemma (a) may disappear to a very great extent {h) without the occur- 
rence of any atrophy whatever of the connective tissue between the 
mnscle-bundles. The nuclei (cj of the connective tissue may even be 
increased in number. 

12 




-Juvenile uiusculai- ati upby. 
observed by de Souza.) 



18-i 



THE RETROGRADE CHANGES. 



In atrophy of the kidney the epithelial cells of the urinary tubules 
(Fig. 50, /) become smaller and may finally wholly vanish so that the 
tubules collapse. Likewise, the epithelium of the glomeruli {d) is lost, 
while the capillaries become obliterated. 

The same thing occurs in simple atrophy of the liver, in that all the 
liver- cells of a lobule may disappear without any perceptible decrease of 
the suj)portiDg reticulum. Likewise the ganglion cells of the brain and 
spinal cord may atrophy without the neuroglia being diminished, ^^"ot 
infrequently the latter may become increased. 

In atrophy of the bones the true bone-tissue becomes diminished, 
while the bone-marrow in excentric atrophy and osteoporosis becomes 

increased. Moreover the 
fat in the cells of the mar- 
row may also vanish, so that 
free spaces are formed which 
become filled with fluid. 

In atro]3hy of the lymph - 
glands and of the spleen the 
free cells in particular dis- 
appear and in parts are com- 
pletely absent. 

The changes leading to 
atrophy may take place with- 
out the occurrence of any 
apparent change of structure 
in the individual tissue-ele- 
ments (Fig. 49), so that the 
condition of atrophy is 
reached essentially through 
a loss of volume of the in- 
dividual parts. Both the 
cell-bodj^ and the nucleus 
may become smaller; and 
the latter change may be ob- 
served particularly in the 
liver in cases of starvation - 
atrophy (Lukjanow). This 
form of atrophy is known 
as simple atrophy, and is 
to be distinguished from the 
degenerative atrophies, in 
which the tissue -elements 

Fig. 47.— Excentric atropby of the lower end of the tibia and during the progress of the 

fibula, with osteoporosis. (Natural size.) atrophy shoiv changes ill their 

structure, and frequentl}^ 
contain pathological substances. Thus a cell may become granular, 
and undergo fragmentation, or may swell up and liquefy, or there 
may be formed within the cell drops of fat or mucus ; all of these 
changes signifying degenerative conditions of the cell-protoplasm. 
These processes are classed as special forms of degeneration and will be 
discussed in the paragraphs of the following section. Degenerative 
changes can occur at the same time in the nuclei, as shown by fragmen- 
tation, distorted shape, clumping of the chromatin, diffusion of chro- 
matin into the cell-protoplasm, swelling and liquefaction of the nucleus.. 




ATROPHY. 



185 



All these processes lead ultimately to the disappearance of the nucleus 
and the destruction of the cell. 

The degenerations leading ultimately to a condition of atrophy of the 
affected organ are of verv frequent occurrence, particularly in glandular 




Fig. 48.— Senile atrophy of the skull-cap, with defect of the external table and the spongy portioa 
throughout the central portion of both parietal bones. 

organs. The process is often complicated by the occurrence of inflam- 
mation. 

According to their genesis the forms of atrophy may be classed as 
active or passive. In the former the cell is no longer able to make use 
of the food brought to it; in the latter the food is either not supplied to 
the cell in sufficient quantity or in the proper form, or harmful sub- 
stances are brought to the cells whicli impair their function. Active 




Fig. 49.— Section of an atrophic muscle, from a case of progressive muscular atrophy. (Miiller's 
fluid, Bismarck brown.) a. Normal muscle-flbres; b, atrophic muscle-flbres ; c, perimysium internum, the 
nuclei of which, at Cj, seem to be increased in number. X 200. 

atrophy is particularly a part of senile degeneration (see above), but it 
occurs also under pathological conditions, especially in the case of nerves, 
glands, and muscles (Fig. 46) whose functional activity is not called into 
play. 

The clinician ordinarily prefers another classification of atrophy; 



186 



THE RETROGRADE CHANGES. 



namely, senile atrophy, atrophy due to Impaired nutrition, pressure 
atrophy, atrophy of disuse, and neuropathic atrophy. 

Senile atrophy (Fig. 48) is partly active, and partly passive, in that 
it is not simply the result of the diminishing vital energy of the cell, but 

also depends in part upon 
the narro>Ying and obliteration 
of the vessels conveying nour- 
islmient to the cells. It may 
occur in all the organs, but is 
often more marked in one 
organ than in another. The 
bones, kidneys, liver, brain, 
and heart may undergo a 
marked loss of volume. 

Atrophy due to impaired 
nutrition may result in the 
first place from an insufficient 
supply of food to the body as 
a whole, or from extensive 
loss of the fluids of the body. 
In these cases the whole body 
is affected, though the fat, 
blood, muscles, and the ab- 
dominal organs suffer to a 
greater extent than the re- 
maining tissues. Local atrophies may result from local disturbances of 
circulation (Fig. 51), and are the frequent sequelae of diseases of the 
Mood-vessels. Further, they are of frequent occurrence as a result or a 
part of inflammatory processes; but it should be noted, that in these 
cases the condition is not of the nature of a simple atrophy, but rather 
of various degenerative changes leading to the death of the cells and of 
the tissues. 

At times atrophy results from the presence of deleterious substances 
in the blood. For example, iodiae causes a diminution in the size of the 




Fig. 50.— Senile atrophy of the kidney. (Alcohol, alum- 
carmine.) a. Normal urinary tubules ; b, normal glomeru- 
lus ; c, stroma with blood-vessels ; </, atrophic and obliter- 
ated glomerulus ; e, small artery, with thickened Intima ; /, 
atrophic and collapsed urinary tubules. X 200. 




Fig. 51.— Arteriosclerotic atrophy of the kidney. (Natural size.) 



thyroid gland. In chronic lead-poisoning the extensor muscles of the 
forearm in particular become atrophic. 

Pressure=atrophy occurs when a tissue is subjected for a length of 
time to a moderate pressure (Fig. 52). It depends partly upon direct 
injury to the tissues and partly upon disturbance of the circulation. 
The most typical examples are : the atrophy of the liver caused by the 



ATROPHY. 



187 



pressure of the edge of the ribs upon the organ due to tight-lacing (^'cor- 
set-liver^'), and the disappearance of bone (Fig. 52) following the press- 
ure of an aortic aneurism, tumors, or of 
an accumulation of fluid in the ventricles 
of the brain. 

Atrophy of disuse occurs in the mus- 
cles, glands, bones, skin, and other tissues, 
and is dependent upon the disuse of the 
organ in question. In the case of muscles 
and glands the atrophy is essentially ac- 
tive; the nutritive processes diminishing 
as the result of the lessened functional 
activity; moreover, the consequent dim- 
inution of the circulation through the part 
is not without effect. In the other tissues 
the atrophy is essentially dependent upon 
the lowering of nutrition of the disused 
parts, though a change in the power of 
assimilation of the cells cannot be wholly 
excluded. When the inactivity occurs 
during the period of development, and 
the tissue as a result becomes stunted, the 
condition is to be regarded as a hypo- 
plasia, though no sharp line can be drawn 
between hyx)oplasia and atrophy, since in 
the former there may be also a disappear- 
ance of structures which had undergone a 
certain degree of development. 

Neuropathic atrophy is a result of 
diseased conditions of the nervous system, 
and is apparent most often in a rapid at- 
rophy of the nerves and muscles, though other tissues may be affected. 

For example, after destruction 
of the anterior horns or of the motor 
roots of the spinal cord, there fol- 
lows an atrophy of the correspond- 
ing nerves and muscles. After in- 
jury of the peripheral nerves the 
skin often becomes atrophic. Ac- 
cording to many authors, disease of 
the nerve -trunks of one side of the 
face is followed by a unilateral neu- 
ropathic facial atrophy (Fig. 53), but 
by others (Mobius) the neuropathic 
nature of this condition is contested. 
Unilateral affections of the brain in 
foetal life or during childhood may 
lead to atrophy of the opposite side 
^ ^ . , ^ . , of the body (congenital and infantile 

Fig. 53.— Facial hemiatrophy. After Lichtheim i • ^ i \ 

and Borel.) hemiatrophy). 




Fift. 52.— Pressure-atrophy of the spinal 
column, due to pressure by aortic aneur- 
ism. 




188 



THE RETROGRADE CHANGES. 



Literature. 

(^Atrophy.) 

Borel: Contribution a I'etiide des asvmetries du visage. These de Berne, Geneve, 
1885. 

Charcot: Maladies des vieillards. Q^uvres compl., vii. 

Coen: SuU' inanizione acuta. Bull, delle Scienze Med. di Bologna, ser. vii., vol. 1,, 
1890. 

Demange: !6tude clinique ct anatomo-patliologique sur la vieillesse, Paris, 1886. 
Demme: Hemiatropliia facialis, xxii. Ber. lib. d. Thatigkeit d. Kinderspitals, Bern, 
1885. 

Flemming: Ricbtungsfigur im Ei bei Untergang d. Follikel. Arch. f. Anat., 1885. 

Herz: Hemiatroph. fac. progressiva. Arch. f. Kinderheilk. , viii., 1887. 

Homen: Zur Kenntniss der Hemiatrophia facialis. Xeurol. Cbl., 1890; Festskrift 

frau Patliologisk-Anatomiska Institutet, Helsingfors. 1890. 
Jarotzky: Verand. d. Pankreaszellen bei Inanition. Virch. Arch., 156 Bd., 1899. 
Josepli: Trophische Xerven (Haarausfall nach Xervenexcision). Virch. Arch., 107 

Bd., 1887. 

Leviii: Halbseitige Gesichtsatrophie (Zusammenstellung der publ. Falle). Charite- 
Annalen, ix. 

liukjanow: L'inanitiou du no3'au cellulaire. Rev. scientif. Paris, 1897. 

Merkel: Die Gewebe beim Altern. Verh. d. X. internat. med. Congr., ii., Berlin, 1891. 

Morpurgo: De la nature des atrophies par inanition. Arch. ital. de. biol. xii., 1889; 

Karyometrische Untersuchungen bei Inanition. Virch. Arch., 152 Bd., 1898. 
Mobius: Der iimschriebene Gesichtsschwund, Wien, 1895. 

Muhlmanii : Die Veranderungen im Greisenalter. Cbl. f. allg. Path., xi., 1900 (Lit.). 
Notzel: Rlickbildung der Gewebe im Froschlarvenschwanz. Arch. f. mikr. Anat.,45 
Bd., 1895. 

Penzoldt: Hemiatrophia facialis. Miinch. med. Woch., 1886. 
Pfitzner : Zur path. Aiiat. d. Zellkerns. Virch. Arch., 103 Bd., 1886. 
V. Recklinghausen: Handb. d. allg. Path. d. Kreislaufs u. d. Ernahruns:. Stuttgart, 
1893. 

Salvioli: Sulla pretesa influenza trofica di nervi. Arch, per le Sc. Med., 1896. 

Seeligmiiller : Gesichtsatrophie. Eulenburg's Realencyklop., 1895. 

Stier: Verhalten d. Musk. u. Xerven nach Las. d. Xervensvst. Arch. f. Psych., 29 

Bd., 1897 (Lit.). 
Voit: Handb. d. Phvsiol. v. Hermann, vi., Leipzig, 1881. 

See also § 23. ^ 



V. Cloudy Swelling and Hydropic Degeneration. 

§ 54. The term cloudy swelling or parencliymatous degeneration or 
gramdar degeneration is applied to that form of cell -degeneration which is 
characterized histologically by a swelling and enlargement of the cells 
due to the formation within the cell -protoplasm of 
free granules, which according to their microchemi- 
cal properties (solubility in acetic acid, insolubility 
in alkalies and ether) are to be regarded as albumin- 
ous bodies. The epithelial cells of the kidney and 
liver (Fig. 54), and the cells of heart-muscle frequent- 
ly show this degeneration, thereby acquiring a cloudy 
appearance, as if covered with dust, while at the same 
time their normal structure and form are lost. Thus, 
for example, in cloudy swelling of the kidney-epi- 
thelium the rod-like markings of the protoplasm are 
lost (Fig. 55, a), as are also the cell -processes pro- 
jecting into the lumen of the tubules. The swollen cells (b, c, d) are 
larger, more plump, and contain dark granules. This change is to be 
regarded as a disorganization of the protoplasm following an absorption 




Fig. 54.— Cloudy swell- 
ing of liver-cells (scraping 
from the cut surface of 
the liver of a man dying 
of septicsemia, examined 
in normal salt solution.) 
X 350. 



CLOUDY SWELLING. 



189 



of fluid, and leads to partial separation of the solid and liquid con- 
stituents of the protoplasm. At the same time the nucleus swells and 
undergoes disorganizcdion. 

Eecovery is possible at a certain degree, and the cells may be re- 
stored to their normal condition. In other cases the cell body is de- 




FiG. 55.— Cloudy swelling of kidney epithelium. (Chromic acid, ammonia, glycerin.) a, Normal 
epithelium ; h, beginning cloudy swelling ; c, advanced stage of cloudy swelling : d, desquamated degen- 
erated epithelium. X 600. 

stroyed, breaking up into granular fragments. Fatty degeneration very 
often accompanies cloudy swelling. 

Cloudy swelling may occur in the cells of any of the parenchymatous 
organs, as the liver, kidneys, or heart, during the course of the majority 
of the infectious diseases, particularly in scarlet fever, typhoid, small- 
pox, erysipelas, diphtheria, septicaemia, etc. The affected organs pre- 
sent a cloudy, dull-shining, often gray appearance ; in marked cases the 
organ may appear as if cooked, the blood -content is \'^ery slight, the con- 
sistency doughy, and the finer details of structure are lost. 

Literature. 

{Cloudy Swelling.) 

Benario: Die Lehre von der triiben Schwellung, Wiirzburg, 1891. 
Galeotti: Ueber die Granulationen in den Zellen. Monatsschr. f. Anat., xii., 1895. 
liukjanow: Grundziige eiuer allgem. Patliologie der Zelle, Leipzig, 1891. 
Schilling: Verlialten der Altmanu'schen Granula bei der triiben Scliwellung. Vircli. 
Arch., 135 Bd., 1894. 

Schmaus u. Bohm: Befund in der Leber bei Pliosphorvergiftung. Vircli. Arch., 
152 Bd., 1898. 

Theohari: Structure des cellules gland, a I'etat pathol, Paris, 1900. 
Verworn: Der kornige Zerfall. r*fliiger's Arch., 63 Bd., 1896. 

Virchow: Cellularpathologie. Arch., 8 Bd., 1855; Reizung u. Reizbarkeit, lb., 14 
Bd., 1858. 



190 



THE KETKOGKALE CHANGES. 



Waldeyer: Yeranderiingen der quergestr. Muskelfasern. Yivcli. Aixli.. 34 Bd., ISO."), 
Zenker: Ueb. d. Veranderung d. ^villkurliclieii Muskeln bei Typhus abdoiii., ].ei]:i7.ii:', 
1864. 

§ 55. Hydropic degeneration is that form of degeneration freqnently 
observed in cells of different kinds, whereby they become swollen through 

the imbibition of fluid. 



When epithelial cells undergo 
this change the cell-contents 
appear clear, the gi-anules of 
the protoplasm are pressed 
farther apart by the fluid, 
often being crowded into a 
ring at the periphery of the 
cell ; the cells thus coming to 
resemble i3lant-cells to a cer- 
tain extent. Vacuoles (Fig. 
56, Z>) — that is, globules of 
clear fluid — may often be 
formed within the cells. The 
nucleus (c) also swells and be- 
comes changed to a large blad- 
der-like vacuole containing 
clear fluid. In muscles show- 
ing hydropic degeneration clear droplets of fluid appear between the 
fibrillte, pushing the latter apart (Fig. 57, 58, a, and Fig. 66, c). 
Through an abundant formation of such droits the muscle fibres may 
acquire in places an appearance of foam-like bubbles (Fig. 57). At first, 
the muscle fibres between these drops remain preserved, but finally they 
undergo fragmentation and lique- 




FiG. 56.— Hydropic degeneration of epithelial cells from 
a carcinoma of the breast. (Miiller's fluid, aniline brown.) 
a. Unchanged epithelium ; /j, hydropic cells containing 
bladder-like drops of fluid [physaUdes]; c, hydropic nuclei; 
d, enlarged nucleoli ; e, wandering cells. X 300. 



faction. 

Hydropic degeneration of cells 
maybe the result of oedema (Figs. 
57 and 58) ; it occurs also in inflam- 
matory foci (Fig. 66) and in tumor- 





I 



Fig. 57.— Hydnipic degeneration of muscle-fibres 
from the calf muscle in chronic oedema of the leg. 
(Flemming's solution, safranin.) X 45. 



Fio. 58. — Transverse section of a muscle- 
bundle sliowinsr hydroinc d(^<j<Mi(M'ation of its 
fibres, oriiller's fluid, hivmatox vim.) o. Muscie- 
flbre with small drops of fluid ; muscle-Iibi-e 
with large dr ips. x 66. 



cells (Fig. 56). In the case of inflammation the degenerative character 
of the process is more marked than in the case of oedema ; and a complete 
liquefaction of the cells and nuclei may result. In oedema the cells, in 
spite of their hydropic condition, may remain alive for a long time. 



VI. Lipomatosis, Atrophy of Fat=Tissue and Fatty Degeneration. 



§ 56. Certain tissues of the human body contain normally a certain 
amount of fat, which deposited in cells is heaped up in such amounts as 



FATTY INFILTRATION. 



191 



to be easily recognizable by the naked eye. This fat is a deposit which 
arises either from the fat ingested, or from fat formed within the body 
ont of albumin and carbohydrates and then deposited in the tissues. 

If the amount of fat taken in or produced within the body is abnor- 
mally great, or if the organism is not able to make proper use of the fat 
ingested or elaborated in the tissues, there arises a disturbance of the 
balance between fat-production and fat-consumption, in favor of the 
first, so that there results an increase in the storing-up of fat. This may 
finally reach such a degree that the functions of the organs concerned 
may be impaired, and the condition must therefore be regarded as path- 
ological. Such an excessive accumulation of fat is designated obesity or 
adipositas or lipomatosis. 

The increased deposit of fat occurs first in the normal fat-depots, the 
panniculus of the skin and serous membranes, the bone-marrow, and 




Fig. 59.— Fatty liver from a case of pulmonary tuberculosis. (Flemmlng's solution, safranin.) a. 
Central portion of the liver-lobule ; t», peripheral zone containing fat ; c, periportal connective tissue. X 30. 

under certain conditions also in the liver (Fig. 59, h). Later the fat is 
deposited in places which normally contain none, as for example, in the 
connective tissue between the muscle-fibres of the heart, in the endocar- 
dium of the ventricles and auricles, and in the intermuscular connective 
tissue of the skeletal muscles (Fig. 60), etc. 

In connective-tissue cells and in liver-cells the fat is deposited in the 
form of small droplets (Fig. 62, a, b), which usually soon, coalesce to 
form larger drops, so that the cells become changed into globular masses 
of fat. 

The pathological deposit of fat may be due either to a congenital 
predisposition or to especial pathological conditions of life. Lipomatosis 
due to a congenital predisposition may be manifested as a general obesity, in 
which the fat throughout the entire body is increased, or the increase 
may be confined to certain areas. In the latter case (the tumor- like 
accumulations of fat being excepted) the excessive deposit of fat is most 
frequently localized in the muscles of the lower extremities (Fig. 60), 
which thereby increase in volume, but at the same time lose a part of 
their fibres (atrophia musculorum lipomatosa pseudohypertrophica). 



192 THE RETROGRADE CHANGES. 

Among the conditions of life which lead to a pathological accumulation of 
fat are: first, a luxurious mode of living ^ further, wasting of bodily strength, 
nnd marasmus, such as is observed especially in chronic tuberculosis. In 




Fig. 60.— Lipomatosis of the calf muscles, associated with atrophy. (Miiller's fluid, carmine.) a, Trans- 
verse section of normal fibre ; aj, of atrophic fibre ; a^, transverse section of sarcolemma tube containing 
disintegrated contractile substance ; Z>, connective tissue ; c, fat-tissue. X 60. 

the first case the deposit of fat is a general one. In the last, the accumu- 
lation of fat is usually confined to the liver (Fig. 59), the liver-tissue at 
the seat of deposit becoming clear yellowish -gray to a straw-yellow in 
color. In the first case the cause of the fat-deposit is the excess of nutri- 




FiG. 61.— Spinal muscular atrophy with lipomatosis, in ascending atrophy of the anterior uorns of the 
spinal cord. (Miiller's fluid, Bismarck brown.) Section from the calf muscle, a. Transverse section of 
atrophic muscle-flbres ; Z>, perimysium; c, fat-iissae ; d, artery; 6, vein. X 60. 



five material ingested ; in the last case it is the inability of the organism 
to use up in sufficient measure the fat taken in or elaborated within the 
body. 



PATHOLOGY OF ADIPOSE TISSUE. 



193 



Under certain conditions a more marked local fat-deposit may occnr as 
a seqnela to tissne atrophy, as, for example, in the neighborhood of con- 
tracted kidneys, and in muscles (Fig. 61, c), which suffer a progressive 
atrophy {a), as the result of diseases of the spinal cord. 

If through a diminution in the amount of nourishment taken into the 
body, or through a deficient formation of fat within the body, or through 
an increased metabolism, the normal amount of body-fat is lost, the con- 
dition is known as atrophy of the fat=t issue. In the process of absorp- 
tion and decomposition of the fat, the latter becomes broken up into 
small droplets, and the fat-cells are finally converted into small connec- 
tive-tissue cells. If, after the disappearance of the fat the si)aces be- 
tween the shrunken fat -cells become filled with a serous fluid, the fat- 
tissue acquires a translucent appearance similar to that of myxomatous 
tissue; and this condition, which occurs especially often in the pannicu- 
lus of the heart, is designated serous atrophy of the fat-tissue. Occasionally 
pigment may be deposited in the atrophic fat-cells, so that the tissue 
acquires a yellow or yellowish-brown color. This condition is designated 
yellow atrophy of fat-tissue. 

The fat deposited in the body may, in the first place, arise from that ingested, so 
that in dogs fed with mutton-fat there occurs a deposit of mutton-fat {Rosenfeld), and 
the feeding of iodized fat leads also to a deposit of iodized fat in the fat-depots ( Win- 
ternitz). It is ordinarily assumed, particularly with reference to the fat-droplets in the 
chyle, that such fat, finely emulsified, is taken up through openings in the cuticular 
margin of the epithelium of the intestinal mucosa. Against this view is opposed the 
fact that such an absorption of fat by the intestinal epithelium cannot be followed step 
by step. FUmming, therefore, assumes that, in the case of the absorption of fat from 
the intestine, as well as its entrance into the fat-cells, the elements of tliefat are taken 
uphy the cells in the form of soluble combinations, and are converted in the cells by the 
chemical activity of their protoplasm again into fat; and that, further, in atrophy of 
fat-tissue, the fat is chemically split up into soluble combinations and so passed out of the 
cells. According to Connstein, the absorbable fats in the stomach and intestine are for 
the greater part split up; and, through tlie combination of the fatty acids with the 
alkalies present in the intestine, are converted into soluble soaps which are absorbed by 
the epithelium. These soaps are changed in the intestinal epithelium (in the same way 
that the absorbed peptone is again changed to an albuminate) back again to globules of 
neutral fat. The glycerin necessary for this process is absorbed directly from the in- 
testine where it is present in the free state, having been split off from the neutral fats. 

Besides that formed from fat and fatty acids, the organism can also form aud store 
up fats from carbohydrates and albumin. The formation of fat from albumin is denied 
by various authors {Pfluger), but has been established beyond any doubt by different 
'Oljservations (see Lindemann, I.e.). 

According to Voit, the immediate factor in metabolism is not the action of oxygen, 
hut lies in the organization of the cells, the protoplasm of which possesses the power, 
in proportion to the external conditions, to break down complex chemical combinations 
into simpler ones. The albumin brought to tlie cell in a soluble form, and after this tlie 
carbohydrates are the most easily decomposed by the cells, fat with greater ditticulty, 
either that taken in with the food or formed witliin the body from albumin or carbo- 
hydrates. When fat is supplied in excess, or when the activity of the cells is exhausted 
before the fat split off from albumin is further decomposed, there will occur a deposit 
of fat. The same thing will happen when fat and carbohydrates or albumin are sup- 
plied at the same time, if the cells after decomposing the latter are incapable of further 
activity. Increase of food-supply, muscular action, and elevation of body-temperature 
cause an increase in the metabolic activity of the cells, while alcohol, morphine, and 
quinine weaken it. Obesity depends upon a greater assimilation of food than can be 
used by the body. The metabolism in this condition ma}^ either be normal, or may be 
diminished through weakness of the cells or diminution of their number. The cause 
of the increased deposit of fat in anaemic conditions may be explained by the diminution 
of the cell-mass of the body and the consequent weakening of metabolism. The de- 
posit of fat in the cells of the intermuscular connective tissue of atrophic muscle may 
be regarded as due to diminished metabolism in the muscle. 

^ According to Gautier, the decomposition of albumin in the cells is the result of 
their functional activity, and occurs in t wo phases. In the first, the phase of ferment- 



194: 



THE RETROGRADE CHANGES. 



action ^vitll0^t oxidation, or ]i\ drolytic splitting, there are formed from the protoplasm 
urea or analogous combinations (salts of uric acid, kreatin-bodies), and at the same 
time the carbohydrates form the fat-bodies. In the second, the phase of oxidation, the 
sugar and fat disappear, both that formed from albumin and that derived from the in- 
gested food. The carbohydrates are in part oxidized; but the greater part, especially 
during muscular inactivity', are changed into fat through a simple process of ferment- 
action, b}^ which a large amount of carbonic acid is set free. Finalh', the fat-bodies 
are also oxidized and disappear. 

Literature. 

{The F(dhoJo(jij of Adipose Tissue.) 

Connstein: Resorption u. Assimilation der Fette. Med. AVoclie, 1900. 

Dercum: Adiposis Dolorosa. Ref. Hdb. of the Med. Sc., 1900; with McCarthy: 

Amer. Jour, of Med. Sc., 1902. 
Ebstein: Die Fettleibigkeit und ihre Beliaudlung, Wiesbaden, 1892 ; Uber Wasserent- 

ziehuug und anstrengende Muskelbewegungen bei Fettsucht, etc., Wiesbaden, 

1885. 

Erb; Dystrophia muscularis progressiva. Leipzig. 1891. 

Flemming-: Bildung u. Riickbildung d. Fettzelle im Bindegewebe. Arch. f. mikr. 

Auat., vii., 1870; Yirch. Archiv, 52 Bd., 18T1 ; Hvpothesen liber Fettresorption. 

Miinch. med. Woch., 1898. 
Gaule: Das Auftreten von Fett in den Zellen. Arch f. Anat., 1890. 
Gautier: Die Ernahrung der Zelle. Biol. Cbl., xiv., 1894. 
Kaufmann: L'origine de la graisse. Arch, de phj^s., viii., 1896. 

Kisch. Die Fettleibigkeit, Stuttgart, 1888; Eiilenburg's Realeucyklop., Art. Fettsucht, 
1895. 

Lee: L'obesit^. Paris, 1886. 

Lindemann: Ueber patholo^-ische Fettbilduns:. Beitr, v. Ziegler, xxv., 1899 (Lit.). 
Munk, J.: Virch. Arch., 80, 95, and 101 B^d. ; Biol. Cbl., v., 1886; Art. Fette in 
Eulenb. Realencykl. 

Nasse: Fettzersetzuuo- u. Fettanhiiufung im thierischen Korper. Biol. Cbl., vi.. 1886. 
V. Noorden: Pathologic des Stofewechsels, Berlin, 1893; Die Fettsucht, Wien, 1900. 
Oertel: Kritisch-physiol. Besprechung d. Ebstein'schen Behandl. d. Fettleibigkeit, 
Leipzig, 1885. 

Pfliig-er: Verdauung u. Resorption der Fette. Pfluger's Arch., 82 Bd., 1900. 
Preisz: Pseudohypertrophic der Muskeln. Arch. f. Psych., xx., 1889. 
Rosenfeld: Giebt es cine fettige Degeneration? Yerh. d. Congr. f. inn. Med., 1897 
and 1899. 

Voit: Physiologic des allg. Stoffwechsels. Hermann's Handb. d. Physiol., vi., 1881; 

Ursaciieu de^r Fettablagerung im Korper, 1884; Biol. Cbl., vi.. 1886. 
Winternitz: Verhalten von Jodfetteu im Orgauismus. Zeit. f. phys. Chem., 24 Bd., 

1897. 

Zawarykin: Fettaufnahme im Diinndarm . durch Wandcrzellen. Arch. f. d. ges. 
Physiol., xxxi., 1883. 

g 57. Fatty degeneration is that form of cell -degeneration in which 
fat is formed from the albumin of the cell-body — that is, from the albu- 
min of the organism — and appears within the cell in the form of gran- 
ules, droplets, or drops. Cells 
which are in the condition 
of fatty degeneration present 
within their cell -substance 
smcdl or larger droplets, which 
are clear, and highly refrac- 
tive (Fig. 62, c, d, e, /, and 
Fig. 63), insoluble in acetic 
acid, and soluble in alcohol 
and ether. AVith osmic acid 
thev become black (Fig. 64, 
h and Fig. 65, A, B, C); in 




Fig. 62. — Fat-containinir liver- Fio. Fatty 
cells, a and b. Fat-infiltration ; c, d, degeneration of the 
e, /, fatty degeneratiu:i. x 400. heart-muscle. X 350. 



FATTY DEGENERATIOX, 



195 




: /|ii!i§iH;:i 



V" 



that the fat reduces tlie osniium tetraoxide to a black osmium hydrate. 
This reaction is obtained only witli olein and oleic acid, but not with pal- 
mitin and stearin. The number and size of the fat-droplets vary greatly, 
though the largest rarelj^ 
attain great size. Thus 
heart -mnscle in a state of 
fatty de£>-eneration (Fig. 63, 
Fig.' 64.^1) and Fig. 66, b) 
shows, according to the 

degree of degeneration, a ^.wm.sgm'^iiw-; ■ ? .i ,n 
varying number of fat- ll'ijllf||ef?f||^^^ 

droplets which are all small ItllV ''^^vlmMtli ■} ilk \Mm. if 

and only rarely become con- 
fluent, and never form large 
drops. 

A similar appearance is 
presented in fatty degener- 
ation of liver-cells (Fig. 
62, 0, d) and of kidney epi- 
thelium (Fig. 65, A, B), 
only the size of the fat- 
droplets is often not so 
uniform. When the proc- 
ess is far advanced in these 
organs the degenerated 
cells containing fat-drop- 
lets become loosened from 
their connection with the 
neighboring cells and 

broken up into a fatty detritus consisting of fine grannies and droplets 
(Fig. 62,/). 

Fatty degeneration may occur in connective-tissue cells and mnscle 
as well as in epithelium (Fig. 65, B, C, d). When the entire cell-com- 
plex is affected, the condition of fatty degeneration is usually readily 

recognizable by the naked eye; the 
more readily of course, the more 
marked the degeneration, the less 
striking the natural color of the tissue 
involved, and the smaller its blood- 
content. Colorless, transparent tis- 
sues, such as the intima of the heart 
and of the blood-vessels, take on an 
opaque whitish appearance; the corti- 
cal tissues of the kidney become gray- 
ish-white, and in severe cases opaque 
yellowish-white ; the heart-muscle be- 
comes yellowish, sometimes spotted as 
the result of localized areas of de- 
generation (Fig. 64) ; and the vol- 
untary muscles appear pale yelloivish- 
hrown. 

The cells contained in fluids 
(pus) or in coagulated masses of ex- 
udate very frequently undergo a 



Marked fatty degeneration (chronic) of the heart- 
( Flemming's soUitibn, safranin.) Normal muscle; 



Fig. 
muscle. 

I), muscle which has undergone fatty degeneration. X 80. 




Fig. 65. -Fatty degeneration of the renal epi- 
thelium, capillary endothelium, and leucocytes, 
in diphtheria. (Flemming's solution, safranin.) 
A, Urinary tubules with epithelium (a) in a 
state of fatty degeneration, and containing a 
hyaline cast {h) cut transversely ; B, intertubu- 
lar capillary with endothelium showing fatty 
degeneration; C, edge of a glomerulus with 
epithelium (c) showing fatty degeneration, and 
capillaries id) containing fatty cells; e. Bow- 
man's capsule. X 300. 



196 



THE RETROGRADE CHANGES. 



fatty degeneration, 
cells. 



which leads ultimately to the disintegration of the 




Fig. 66.— Fatty degeneration, vacuolization, and disor- 
ganization of the heart-muscle in a patient dying from pneu- 
monia and nephritis. (Flemming's safranin.) a, Trans- 
verse section of normal muscle-cell ; Z), muscle-cell in a state 
of fatty degeneration ; muscle-cells with vacuoles; d, dis- 
organized cell. X 400. 



The causes of fatty degeneration are to be found in a disturbance of 
nutrition due to changes in the hlood-snppJy and in the composition of the 

Mood, and in a lowering of the 
- ^ ^' ^ '^i."-'] mtality of the cells. A chief 
' _ c ^'^^^ played by a x^ersistfut 

diminution of oxygen, as a re- 
' suit of which there occurs an 

^ r.:^' increased destruction of albu- 

min with the formation of 
fat, the nitrogenous end-pro- 
ducts in the urine being at 
the same time increased. Fat - 
ty degeneration is observed, 
therefore, particularly in 
acute aujemia due to hoemor- 
rhage (heart, oi^tic nerve), in 
chronic anaemia and leuktemia 
(heart, liver, intima of the 
blood-vessels), narro^^'ing and 
closure of the arteries (in the 
area supplied by the affected 
vessel), chronic venous con- 
gestion, poisoning with phos- 
phorus, arsenic, chloroform, 
and many forms of mushrooms (heart, liver, kidneys, blood-vessels, 
particularly the capillaries), in manj^ infectious diseases, as diphtheria 
(kidneys, heart, and leucocytes), pneumonia (kidneys, heart) (Fig. 66, 
h), chronic ulcerative pulmonary tuberculosis (kidneys). 

In the infectious diseases the fatty degeneration occurring in the 
glandular organs, the 
leucocytes and the heart, 
may be attributed pri- 
marily to the effect of 
the poisons of these dis- 
eases; but an increased 
body temperature, if 
prolonged, may also pro- 
duce fatty degeneration 
of the organs. 

Cells which have be- 
come loosened from their 
natural position, and are 
exposed to new condi- 
tions of nutrition — as, 
for example, leucocytes 
which have escaped from -pio. 
the vessels in the course b^^^^- 
of an inflammation, des- 
quamated epithelial cells and loosened connective-tissue cells — also verj- 
frequently undergo fatty degeneration. Further, in regenerative and 
inflammatory proliferations and in tumors, especially in carcinoma, a 
large part of the cells may die after passing through the stage of fatty 




67.— Fat-granule ceils in an anfemic area of softening in the' 
(Marchi"s fluid.) a. Fat-granule cells ; ?j, blood-vessels, x 280. 



FATTY DEGENERATION. 



197 



degeneration, for the reason that in these cell -masses there is an insuffi- 
cient supply of nutrition. 

In the majority of cases fatty degeneration is the only histological 
change which can be demonstrated in the cells, but it is at times asso- 
ciated with other degenerative changes. The most frequent combination is 
that of cloudy swelling and grannlar disintegration tvith fatty degeneration ; 
but hydropic degeneration ivith vacuole formation (Fig. 66, c) may also occur 
at the same time with fatty degeneration. Both of these combinations occur 
especially in cases of poisoning and in inflammations. Moreover, fatty 
degeneration of the cells accompanies many degenerations of the ground- 
substance, as, for example, amyloid degeneration of the connective tissue 
(see § 63, Fig. 81). 

The question whether the fat found in the cells is a degeneration or a deposit is in 
many cases very difficult and uncertain of answer; and it often cannot be determined 
in a given case whether there is a true fatty degeneration present, in the sense that the 
fat is formed in the cell out of the cell-albumin. In general, fatty degeneration is as- 
sumed to be present when fat is found in cells which ordinarily contain no fat, and 
when clinically there is apparent a diminution of functional activity, and anatomically 
a degeneration of cell-structure. It must be noted, however, that careful investiga- 
tions {Unna, Sata) have shown, that many cells even under normal conditions contain 
fat more frequently and regularly than has been generally supposed (for example, the 
epithelium of the sweat-glands and lachrymal gland, and of the epidermis, and also car- 
tilage cells). Moreover, both in fcetal tissues and in proliferating cells (not degenerat- 
ing) with cell-division figures, fat is often present. Under conditions, in which the 
assumption of a weakening and degeneration of the organ concerned is well founded, 
nothing further may be recognized by which it is possible to say whether the fat pres- 
ent has arisen from the albumin of the affected cells, or whether it has been produced 
from carbohydrates or from the lecithin of the cells, or out of substances brought to 
the cells from without. For this reason we should not go so far as to deny the occur- 
rence of a true fatty degeneration, that is, a formation of fat out of the cell-substance 
(Eosenfeld) ; but in the diagnosis of cells showing fatty degeneration we must at times 
bear in mind the different possibilities of the origin of the fat. 

Requiring a special consideration are certain round cells of different size, which 
are entirely filled with fat droplets, and are therefore known as fat=granule globules or 
fat=granule cells (Fig. 67, a). They occur especially in degenerative processes in the 
brain and spinal cord ; and have been repeatedly regarded as tissue-cells which have 
undergone fatty degeneration, in the brain as ganglion-cells and glia-cells presenting thia 
degeneration. The true fat-granule globules or cells are, however, not the fixed tissue- 
cells which have become fatty, but are amceboid leucocytes and tissue-cells arising through 
proliferation, which through phagocytic action have taken up into their substance the fatty 
detritus arising from the disintegration of tissue. According to Arnold, the fat-granules 
also arise through the conversion of plasmosomes into fat. 

According to the investigations of Lindemami, the fat arising through degeneration 
of the heart-muscle differs essentially from the fat deposited in the heart or in the subcu- 
taneous tissue. The degeneration-fat is able to take up 108.55 per cent of iodine, nor- 
mal heart-fat only 61.1 per cent, the content in free fatty acid amounting to 18.35 as 
against 7.3 in normal heart-fat. 

Literature. 

{Fatty Degeneration. ) 

Arnold: Fettkornchenzellen- und'Granulalehre. Anat. Anz., xviii., 1900. 
AschofF: Fettgehalt fotaler Gewebe. Cbl. f. allg. Path., viii., 1897. 
Beneke: FettemboHe. Beitr. v. Ziegler, xxii., 1897. 

Binz u. Sehulz: Kohlenoxydgasvergiftung. Arch. f. exp. Path., xiv., 1881. 
Ehrlich: Das Sauerstoffbediirfniss des Organismus, Berlin, 1885. 

Elbe: Hist. Unters. iiber Jodoform u, Arsenintoxication. Inaug.-Diss., Rostock, 1899, 
Frankel: Eiofluss d. verminderten Sauerstoffzufuhr auf den Eiweisszerfall. Virch. 
Arch., 67 Bd., 1876. 

Handwerck: Verb. d. Fettkorper zu Osmiumsaure u. Sudan. Zeit. f. wiss. Mikr.^ 
XV., 1898. 



198 



THE RETROGRADE CHANGES. 



V. Kahlden: Aetiologie imd Genese der Nephritis. Beitr. v. Ziegler, xi., 1892. 
KreM: Fettige Degeneration des Herzens. Deut. Arch. f. kliii. Med., 51 Bd., 1893. 
Leo: Fettbildung u. Fetttransport bei Phosphorvergittung. Zeitschr. f. phys. Chem., 
ix., 1885. 

Leyden ii. Munk: Die acute Phosphorvergiftung, Berlin, 1865. 

Lindemann: Ueber pathologische Fettbildung. Beitr. v. Ziegler, xxv., 1899 (Lit.); 
Wirkung des Oleum Pulegii. Arch. f. ex p. Path., 32 Bd., 1896; Zeit. f. Biol., 39 
Bd., 1900; Das Fett des normalen u. des fettig entarteten Herzmuskels. Zeit. f. 
Biol., 38 Bd., 1899. 

Lubarsch: Fettdegeneration u. Fettintiltration. Ergebn. d. ailg. Path., iii., 1897. 
Lukjanow: Vorles. liber die allgem. Path, der Zelle, Leipzig, 1893. 
Lummert: Thierische Fette. Pfliiger's Arch., 71 Bd., 1898. 
Michaelis: Milchsecretion. Arcli.'f. mikr. Anat., 51 Bd., 1898. 

Runge : Die Krankheiten der ersten Lebenstage (acute Fettdegeneration), Stuttgart, 
1893. 

Sacerdotti: Knorpelfett. Virch. Arch., 159 Bd., 1900. 

Sata: Fettbildung durch verschiedene Bakterien. Cbl. f. allg. Path., xi., 1900; Ueber 
das York, von Fett in der Haut u. in einigen Driisen. Beitr. v. Ziegler, xxvii. ; 
Fett in patholog. Geweben, ib., xxviii., 1900. 

Schmaus: York. d. osmirten Fettes in d. Leber bei Phosphorverg. Mlinch. med. 
Woch., 1897. 

Schulzen u. Riess: StolTumsatz bei Phosphorvergiftung. Ann. d. Charite-Kranken- 
hauses, xv. 

Starke: Ueber Fettgranula. Arch. f. Anat. u. Phys., 1895. 

Steinhaus: Morphologic der Milchabsonderung. Arch. f. Anat., 1892.- 

Taylor: Lipogenesis. Amer, Journ. of Med. Sc., 1899; Journ. of Exp. Med., 1899; 

On Fatty Degeneration. Joui-n. of Med. Res., 1903. 
Unna: Nachweis d. Fettes in der Haut. Monatsh. f. prakt. Derm., 1898. 
Weber, H. : Fettige Entartung des Herzens. Yirch. Arch., 12 Bd., 1857. 
Wentscher: Eigenleben menschl. Epidermiszellen. Beitr. v. Ziegler, xxiv., 1898. 
Werbowsky: Wirkung erhohter Eigenwarme. Beitr. v. Ziegler, xviii., 1895 (Lit.). 
Weyl u. Apt: Fettgehalt pathologischer Organe. Virch. Arch., 95 Bd., 1884. 
Ziegler u. Obolonsky: Arsenikvergiftung u. Phosphorvergiftung. Beitr. v. Ziegler, 

ii., 1888. 

§ 58. The fats which occur in the human body consist almost entirely 
of a mixture of the glycerin -esters of oleic, palmitic, and stearic acids 
which are designated olein, pahnitin, and stearin. The first is fluid at 
ordinary temperatures, the second melts at 46°, the third at 53° 0. 
Since the body-fats contain varying proportions of olein, palmitin, and 
vStearin, they vary in consistency and melting-point. As fat is not solu- 
ble in water or watery fluids, the fat in the body, either free or enclosed 
within cells, is not dissolved in the tissue -fluids. At most, only traces 
of it are dissolved in the blood, lymph, chyle, and bile, which contain 
small amounts of soaps. If after death the fat-containing tissues of the 
body are cooled below the melting-point of the contained fat, the stearin 
and palmitin may separate and form fine stellate or feathery needles 
(Fig. 68, h, c, d), which are commonly called margarin needles, and 
which, according to the conditions, are found sometimes in fat-cells, at 
other times free in the tissue-fluids. 

Cholesterin occurs in the form of delicate rhombic plates (Fig. 68, 
a), the edges and corners of which are often notched. These may be 
found wherever there are formed masses of detritus containing fat, aris- 
ing from degenerating cells or extravasations of blood, as in the diseased 
tunica vaginalis of the testis, in a dilated sebaceous duct or gland, or in 
a softened area of degeneration in the wall of a diseased aorta. When 
the substance in which the cholesterin plates are formed is fluid, these 
may often be visible to the naked eye as little glistening scales. 

Cholesterin is a constant constituent of the bile, and is furnished by 
the mucous membrane of the gall-bladder and bile-ducts, and held in 
solution by the bile salts and soaps. It is found also in the medulla of 



CHOLESTERIN, GLYCOGEN. 



199 



the uerve-fibres, and iii small amounts in the blood, where it is held in 
solution by fats and soajDS. According to Burchard traces of cholesterin 
are found in all the organs. 

Cholesterin is insoluble in water, dilute acids, caustic alkalies, and 
cold alcohol; it is soluble in boiling alcohol, ether, chloroform, and 
benzol. 

When treated with a mixture of five parts of concentrated sulphuric 
acid and one part of water the edges of cholesterin crystals take on a 
carmine -red color, which gradually passes into violet. Sulphuric acid 




Fig. 68.— a, Cholesterin plates ; b, free cluster of margarln needles ; c, needles enclosed within fat-cells ; 
ci, grass-like bunch of margarin needles. X 300. 

and water mixed in the proportions of three to one give a violet color to 
the edges of the crystals. Concentrated sulphuric acid containing a trace 
of iodine colors the crystals violet, blue, green, and red. 

The origin of cholesterin is not known with certainty. It is probable 
that it is an intermediate product in the decomposition of albumin. Cor- 
responding to this view, it is found under those pathological conditions 
in which albuminous substances break down with the formation of fat. 



Literature. 

(CJiolesterin.) 

Hoppe-Seyler ; Handb. d. pliysiol. u. path.-chem. Analyse, v. Aiifl. 

Munk: Art. Cholesterin, Eulenbiirg's Realencjidop. u. Eulenburg's Jahrbucli, i., 

Vn. The Deposit of Glycogen. 

§ 59. Glycogen is a carbohydrate which is readily convertible into 
sugar; and in the body is formed chiefly from the carbohydrates of the 
food, but may also be formed from albumin and gelatin. 

In the tissues of the body glycogen is found as a hyaline substance, 
most often within the cells, but occasionally in the tissue-spaces. It 
usually occurs in the form of spherules of different sizes. In the cells 
these spherules are most frequently found in the neighborhood of the 
nucleus. 

Glycogen is soluble in water, but the solubility of that found in dif- 
ferent tissues varies (Langhans) ; that found in the liver, kidneys, mus- 
13 



200 



THE RETROGRADE CHANGES. 



cles, and pus- corpuscles is more easily soluble than that of cartilage- 
cells and surface epithelium. Fixation of the tissue in alcohol renders 
the glycogen less soluble in ^Yater. After death the glycogen of the 
liver is quickly converted into sugar through the action of a diastatic 
ferment. 

Glycogen becomes brownish -red tclien treated icith iodine. In order to 
avoid the solution in water of the glycogen contained in fresh j)repara- 
tions, a syrui)y mixture of gum and iodine (Ehrlich), or glycerin to 
which iodine has been added (Barfurth) may be used when it is desired 
to test for this reaction. Sections of tissues fixed in alcohol give best re- 
sults (Langhans) when treated with dilute tincture of iodine (one part 
tincture of iodine, four parts absolute alcohol), and cleared with oil of 
origanum, in which the reaction remains i^reserved for a long time. 

Glj^cogen is present in almost all the tissues of the embryo, also in 
the foetal membranes at an early period of development; and in the 
adult body in the liver-cells, muscles, heart-muscle, cartilage cells, epi- 
thelium of the body of the uterus, portio vaginalis and vagina (Lang- 
hans), in the leucocytes, and in the blood-serum (Gabritschewski). 
During starvation the glycogen of the liver is diminished, and under 
pathological conditions may wholly disai^iiear. 

In diabetes the epithelial cells of the kidneys show a very rich de- 
posit of glycogen, particularly those of the loops of Henle. In the isth- 
mus of the latter the cells are almost wholly filled with glycogen. If 
this be dissolved out with water, the cells appear as clear vacuoles. In 
the blood of diabetic individuals the glycogen, both the intracellular and 
extracellular, is increased. 

In fresh inflammatory exudates glycogen is present in the pus-cor- 
puscles. According to the investigations by Brault all tumors, carcino- 
mata and sarcomata, exhibiting rapid growth contain large amounts of 
glycogen in their cells, so that these contain large vacuoles. In slowly- 
growing tumors or in those whose growth is at a standstill, or in those 
showing beginning degeneration (fatty), glycogen is not present. The 
tumor-cells form the glycogen, and its presence is not to be regarded as 
an evidence of degeneration, but rather as a sign of good nutrition and 
luxuriant cell -growth. 

Literature. 

{Ghjcogen.) 

Barfurth.: Histochem. Untersuch. liber das Glvkogen. Arch. f. mikr. Anat., 25 Bd., 
1885. 

Brault: Glvcogenese dans les tumeurs. Arch, des sc. med., 1896; La production du 
glvcogene dans les tissus qui avoisinent. Arch. gen. de med., 1899; Le pronostlc 
des tumeurs. L'eeuvre med.-chir., 1899. 

Butte: La fonction glycogenique du foie dans quelques maladies. Arch, de phvs., 
1891. 

Czerny: Zur Kenntn. d. fflvkogenen u. amyloidcn Entartung. Arch. f. exp. Path., 
33 Bd., 1893. 

Driessen: Uuters. tiber glykogenreiche Endotheiiome. Beitr. v. Ziegler, xii., 1892. 
Ehrlich: Glvkogen im diabetischen u. im norm. Organismus. Zeit. f. klin. Med., vi., 
1883. 

Gabritschewski : Glykogenreaction im Blute. Arch. f. exp. Path., 28 Bd., 1891. 
Kiilz: Glvkogen. Festschr. d. med. Fac. Marburg f. C. Ludwig, Marburg, 1891. 
Langhans: Glvkogen in pathol. Neubildungen u. Eihauten. Yirch. Arch., 120 Bd. 
1890. 

Marchand: Geschwulst aus quergestr. ]\Iuskelfascrn mit Glvkogen. Virch. Arch., 
100 Bd., 1885. 



MUCOUS DEGENERATION. 



201 



V Merinff- Zur Glvkogenbildung in der Leber. Pflliger's Arch., xiv., 1877; Ueber 

Diabetes inellitus. Verli. d. 6. Congr. f. iun. Med., Wiesbaden, 1887. 
Nebelthau: Glykogenbilduug in der Leber. Zeit. f. Biol, 28 Bd. 1892. 
Wolffberg: Ursprung u. Aufspeiclierung des Glykogens. Zeit. f. Biol., xni., 187b. 



VIII. riucous Degeneration. 

§ 60. riucous degeneration has its physiological prototype in the 
production of mucus by the mucous membranes and mucous glands, and 
in the formation of mucus in the connective tissue of the umbilical cord, 
tendons, bursse, aud synovial membranes, 
mucus occurs as a jelly-like matrix ; in the 
joints, burs^e, and tendon-sheaths it forms 
a clear, stringy fluid. 

In the epithelium of the mucous mem- 
branes the mucus appears first in the gob- 
let-cells (Fig. 69, «), forming a clear sub- 
stance which stains with hsematoxylin. In 
mucous glands, during the process of mu- 
cus formation, the epithelial cells swell, 
their central portions become clear, and 
the granules of the protoplasm are re- 
duced to small groups or strands. The 
so-called mucous corpuscles of the saliv- 
ary secretion, which are characterized by 
glassy, transparent contents and vibrating 
protoplasmic granules, are round cells 
which have undergone mucous degener- 
ation. 

The mucus formed from the protoplasm 
of the cells may be discharged, and the 
cells remain intact, or in other cases they 
may be destroj^ed. 

Mucus is produced in the same way 
under pathological conditions as under nor- 
mal (Fig. 69, a). In catarrh of the mucous 
membranes there is an increased formation 
of mucus by the cells of the superficial epi- 
thelium as well as those of the glands. In addition the pus- corpuscles 
may also undergo mucous degeneration, the mucin being formed from 
the nuclein of the nuclei (Kossel). In mucous membranes covered with 
cylindrical cells the number of goblet-cells is increased, and in the secre- 
tion there are found cells which have undergone complete mucous degen- 
eration — that is, they have been converted into glassy masses containing 
few granules. Other cells contain the mucus in the form of drops of 
varying size. 

The epithelium of pathological tissues may also undergo a mucous 
degeneration, in a manner similar to that occurring in normal tissues. 
Thus the epithelial lining of cysts of the ovary and of intestinal tumors 
may often contain numerous goblet-cells (Fig. 70, a), and cells which 
have undergone total mucous degeneration (b). In the so-called gelat- 
inous or mucoid carcinoma (colloid carcinoma) a large part of the epi- 
thelial cells suffer a mucous metamorphosis. 

Of the connective tissues, which may suffer a mucous de'generation and 



In the umbilical cor< 




Fig. o9.— Formation of mucus within 
the epithelial cells of an adenomatous 
polyp of the small intestine. (Alcohol, 
hsematoxylin.) a. Epithelium with 
dark-stained (hasmatoxylin) drops of 
mucus within the cells ; h, free mucus ; 
c, leucocytes in the epithelium. X 300. 



202 



THE RETROGKADE CHANGES. 



thereby acquire a gelatinous, transj^areut appearauce, may be mentioned 
fibrous connective tissue, also cartilage, bone, adipose tissue, bone -mar- 
row, and sarcomatous tissue. lu these tissues it is chiefly the ground- 
substance (Fig. 71, h) which undergoes mucous change and is converted 
into a homogeneous, structureless mass. Tlie cells may remain un- 
changed, or may become fatty, or also undergo mucous degeneration. 
In the last event the entire tissue ultimately torms a hyaline mass, in 




FKx. 70. Fig. 71. 

Fig. 70.— Epithelial cells wliich have undergone mucous defeneration, from a cystadenoma of the ovarv. 
a, Cells showing slight change ; h, cells showing marked degree of mucous change. X 400. 

Fig. 71— Mucous degeneration of the connective tissue of the aortic valves (osmic acid, glycerin), a. 
Fibrous tissue ; t», myxomatous tissue. X 350. 



which only scattered tibres of connective tissue, or single cells or groups 
of cells are left to suggest the original tissue. 

The stringy, or gelatinous material, which results froaii mucous de- 
generation, does not represent a single chemical substance ; in it there 
may be found different varieties of mucins as well as of pseudomucins. 

The mucins (submaxillary, intestinal, and tendon mucin) are nitro- 
genous substances somewhat resembling albumin. They dissolve or 
swell up in water forming a stringy, mucous fluid, from which they may 
be precipitated in a stringy form by means of alcohol or acetic acid ; but 
differ from the true albumins in the fact that the precipitate is not redis- 
solved in an excess of the acid. The precipitated mucins are soluble in 
neutral salt -solutions, caustic alkalies, and alkaline carbonates ; and are 
gradually converted into alkali-albuminates in case of solution by the 
last named. 

All mucins contain nitrogen and sulphur ; their content in carbon, 
oxygen, nitrogen, and sulphur varies in the different forms. By proi^er 
treatment a carbohydrate, called animal gum (Landwehr, Hammarsten), 
may be split off from the mucins. For this reason mucin may be called 
a glycoproteid (Pfannenstiel). 

Pseudomucin also dissolves in water, forming a gelatinous fluid, 
from which it may be precipitated in stringy masses by alcohol. The 
precipitate redissolves in water. Solutions of pseudomucin are not pre- 
cipitated by acetic acid. Boiling with dilute mineral acids leads to the 
splitting-off of a carbohydrate (as is the case with mucin), which reduces 
copper sulphate in alkaline solution (Pfannenstiel). 

Pseudomucin is found particularly in ovarian cystomata, and is the 
cause of the gelatinous character of the cyst -contents. It is produced 
by the epithelium of these tumors (Fig. 70); and in its formation the 
same changes take place in the cells, as in the formation of mucin from 
epithelium. In all probability the mucous substance present in gelat- 
inous carcinomata is a body closely related to pseudomucin or metalbu- 
min — that is, there are different varieties of pseudomucin (Pfannenstiel), 
of which the two mentioned are examples. 



EPITHELIAL COLLOID 



AND EPITHELIAL HYALINE. 



203 



The muciu-like substances, precipitable by acetic acid, ^vhich (3cciir in the synovial 
fluid, dilTer, according to Salkoicski, from nucleoalbumiu in the absence of phosphorus. 
From ordinary mucin the}' are distinguished by their different behavior with mineral 
acids; wlien boiled with dilute hydrochloric acid no reducing substance is obtained. 

MifjukoTf \ms obtained from the gelatinous contents of an ovarian cyst a mucin-like 
substance which he has named paramucin. It differs from pseudomucin chietiy in the 
fact that without previous boiling with dilute acids it reduces copper oxide in an alka- 
line solution. 

Literature. 

(Mucous Degeneration.) 

Eichwald : Die KoUoidentartung der Eierstocke, Wurzburger med. Zeitschr. , 1864. 
Hammarsten : Studien iiber Mucin u. mucinahnliche Substanzen. Pfliig. Arch., 36 
Bd., 1885. 

Hoppe-Seyler : Handb. d. phys. u. pathol.-chem. Analyse, 5. Aufl. 
Hoyer: Nachweis d. Mucins durch Farbemethoden. Arch. f. mikr. Anat., 26 Bd., 
1890. 

Kossel: Ueber Schleim und schleimbildende Stolfe. Deut. med. Woch., 1891. 
Landwehr: Ueber Mucin, Metalbumin, u. Paralbumin. Zeitschr. f. phys. Chem., 

viii. ; Ueber die Bedeutung des thier. Gummi's. Pfliiger's Arch., 39 Bd., u. 40 

Bd., 1887. 

Leath.es: Beitr. z. Chemie d. Ovarialmucoide. Arch. f. exp. Path.. 43 Bd.. 1899. 
Mitjiikoff: Ueber das Paramucin. Arch. f. Gyn., 49 Bd., 1895. 

Pfannenstiel : Pseudomucine d. cystischen Ovarialgeschwiilste. Arch. f. Gyn.. 38 
Bd.. 1890. 

Salkowski: Zur Kenntniss der Synovia. Virch. Arch., 131 Bd., 1893. 
Struiken: Histol. u. Histochemie d. Rectumepithels u. d. Schleimzellen. Inaug.- 
Diss., Freiburg, 1893. 



IX. Formation of Epithelial Colloid and Epithelial Hyaline 

Concretions. 

§ 61. The epithelial formation of colloid is a i^rocess closely related 
to the epithelial production of mucus ; it consists partly in a secretion of 




colloid by gland-cells, and partly in a conversion of entire cells into col- 
loid. Physiologically, colloid is found in the thyroid (Fig. 72), where it 



204 



THE RETROGRADE CHANGES. 




Fig. 74.— Dilated urinary tubules filled with colloid 
fluid, hsematoxylin, and eosin.) X 250. 



(Miiller's 



appears iu the form of hyaline, 7-ather firm, colorless, or slightly colored, 
jelly-like masses, which in the first place fill the follicles (c), but from 
these may extend into the lymph-vessels of the thyroid. Pathological 

collections of colloid occur 
both in normal gland-tissue 
and in newly-formed gland- 
ular-tissue of pathological 
nature. The accumulation 
causes a more or less marked 
distention of the follicles, 
- thereby leads to an en- 

it^^ ^^^y ^^^^^^^f'^' largement of the affected 

gland, which is known as 
/. - «- y colloid goitre or bronchocele. 

The typical secretion of 
colloid is characterized by 
the formation of homoge- 
neous granules and spherules 
in that i3ortion of the epithelial cells next to the lumen of the follicle 
(Fig. 73). Some of the cells may be completely filled with these gran- 
ules. In excessive and atypical formation desquamated cells may be- 
come converted into the hyaline substance of colloid. 

The colloid of the thyroid is found on microscopical examination to 
be homogeneous ; and according to its appearance it may be designated 
epithelial hyalin. As a rule it incloses no cellular elements, but de- 
generating cells may be found in it. Alcohol and acetic acid cause no 
clouding, or precipitation in the form of threads, as happens in the 
case of mucin when 
so treated. By 
means of Van Gie- 
son's staining meth- 
od the colloid is 
stained orange -red, 
while the connec- 
tive tissue takes a 
fuchsin-red. It must 
be noted that the 
contents of the thy- 
roid follicles, Avhich 
are designated col- 
loid, are not always 
of the same charac- 
ter. At one time 
the substance is firm, 
at another soft or 
even fluid, or at least 
is readily soluble in 
water. In prej^ara- 

tions fixed in alcohol a granulation or cleavage may be caused by con- 
traction ; and the staining reactions are not always the same. 

The chemical nature of the thyroid colloid is not fully known, and it 
is probable that the contents of the follicles are of variable composition. 
It is most probably an albuminoid body which is combined with iodothy- 
rin, the active principle of the thyroid gland. 




Fig. 75.— f'olloid concretions in the cystic dilated tubules of the paro- 
varium. (Formalin, Van Gieson's stain.) a, Gland- tubules of the 
parovarium ; c, cysts containing colloid concretions (d) . X 80. 



EPITHELIAL HYALIN COLLOID. 



205 



Epithelial hyalin is also found in the glands of the hypophysis cere- 
bri, in the urinary tubules of diseased kidneys (Fig. 74), in the prostate 
(Fig. 76, d), in cysts of the parovarium (Fig. 75, d), in the glands of the 
stomach, and more rarely in other glands. In the last-named organs the 
hyalin occurs in the form of a uniformly homogeneous mass completely 




Tig. 76.— Section from a hypertrophic prostate with concretions. (Miiller's fluid, haematoxylin, and eosin.) 
a, Stroma ; b, glands ; c, dilated glands ; d, concretions. X 45. 

filling the gland-lumen, or often as hyaline, in part laminated concre= 
tions (Fig. 75, d, and Fig. 76, d) of more or less firm consistency. 

It must not be assumed that the last-named formations are identical 
in their chemical composition with thyroid colloid. The only thing 
which they possess in common is this : tliey both represeu t transformed 
protoplasm of gland -cells — a substance which is hyaline, possesses a certain 
firmness, and does not react to chemical reagents in the same manner as does 
mucin. These concretions may also undergo changes which necessitate, 
on their part, a different behavior toward microchemical reactions. 
This is ]3articularly true of the prostatic concretions, which not infre- 
quently show, when treated with iodine, a reaction that has been taken 
as evidence that they are composed of amyloid material (see § 64). It 
may be proved, both in the case of prostatic concretions and of renal 
colloid, that they represent cell-material which has become changed into 
hyaline substance. In the case of renal colloid, however, it is only 
under especial conditions that the participation in its formation of albu- 
min derived from the glomeruli may be excluded. 

Colloid is a collective term which is applied to a great variety of formations that 
possess only certain physical attributes in common. There is a very great difference of 
opinion among authors as to the application of the term. Under colloid degeneration, 
for example, von Recklinghausen places mucous, am3^1oid, and hyaline degenerations; 
including under the last-named epithelial colloid-formation, hyaline degeneraition of 
connective tissue, as well as hyaline coagulation-necroses and hyaline thrombi. Mar- 
chand gives the term a more limited application, but includes under colloid certain 
forms of epithelial mucin-formation (particularly in tumors), and also hya^me forma- 
tions in connective tissue. Inasmuch as colloid is not a definite chemical entity, and 
as its staining-reactions do not differentiate it sharply from other hyaline substances, it 
seems to me most expedient to apply the term only to those hyaline products of epithe- 



206 



THE RETROGRADE CHANGES. 



lium which do not possess the characteristics of mucin. 1 have, tlierefore, also classified 
as colloid those epithelial concretions M hich on account of tlieir reaction with iodine 
(brown or blue color when treated with dilute iodine solutions) have hitherto been le- 
garded as amyloid bodies, if objection is made to the classiticatiou of these formations 
as colloid, they may be placed under the heading of epithelial hyalin. 

As epithelial hyalin (keratohyalin?) maybe classed also tha In/ah' /ic rinnmhs mul 
splieniles described hx liiissd, Kkin, and others, and which are found especially in can- 
cer cells. They stain intensel}' with fuchsin, and also with Gram's method or with 
Weigert's fibrin stain. It should be noted further that similar bodies of varying size 
and form have been observed in the epithelium during the development of a vaccination 
pustule {IlUckel), and have been by many regarded as parasites. 



Literature. 

(Colloid.) 

Biondi: Beitr. z. S cruet ur u. Function d. Schllddruse. Berl. klin. Wocb., 1SS8. 
Bozzi: Untersuch. iiber die Schilddrlise. Beitr. v. Ziegler, xviii., 1895. 
Bubnow: Chemische Bestandtheile der Schilddrlise. Zeitschr. f. phvs. Chem., viii., 
1883. 

Ernst: Ueber Hyalin u. seine Bezieh. z. Kolloid, Alrch. Arch.. 130 Bd., 1892. 

Hlickel: Die Vaccinekorperchen. Beitr. v. Ziegler, Supplh., 1898. 

Hiirthle: Secretionsvorgange in d. Schilddrlise. Pflliii-. Arch. f. d. ges. Phvs., 56 Bd., 

1894, 

Klein : Russel-sche Fuchsinkorperclien. Beitr. v. Ziegler, xi. , 1892. 
Langendorf: Beitr. z. Kenutn. d. Schilddrlise. Arch. f. An., Supplh.. 1889. 
Marchand: Kolloidentartung. Eulenburg's Realencyklop. , 1895. 
Pianese: Histol. u. Aetiol. d. Carcinoms. Beitr. v. Ziegler, Supplh., 1896. 
Podbelsky: Kolloid in den Lvmpho-ef. d. Schilddrlise. Prager med. AYoch., 1892. 
Pratt: Goitre. Ref. Handb. of Med. Sc., 1902. 

V. Reckling-hausen: Allg. Pathol, des Kreislaufs u. der Ernahrung, Stuttgart. 1883. 
Reinbach: Bildung des Kolloids in Strumen. Beitr. v. Ziegler, xvi., 1894. 
Russel: Characteristic Organism of Cancer. Brit. INIed. Journ., ii., 1890. 
Virchow: Die krankh. Geschwlilste, iii. Bd., und Ueber d. eigenthliml. Verhalteu al- 

buminoser Fllissio-keiteu bei Zusatz von Salzen. Vi:\ Arch., 6 Bd., 1854. 
Wolfler: Der Bau des Kropfes, Berlin, 1883. 



X. The Pathological Cornification of Epithelium. 

§ 62. The cornification of the surface epithelium over the entire 
skin is a physiological process, characterized essentially by the fact that 
the cells in the outer strata of the prickle layer of the stratum goiuina- 
tiviim undergo a horny change. This cornilication takes place first at 
the x)erii3hery of the cells and in the processes binding the cells together, 
while at the same time the inner portions of the cell and the nnclens 
shrink, so that the cells become changed into thin, flat, horny scales. 
This horny substance or Ir rat in is a very resistant modified albuminoid 
body of homogeneous composition, and is capable of resisting digestion 
by the gastric or pancreatic juices. 

As accompanying phenomena of cornification there appear in the cells 
of the prickle layer peculiar hyaline granules and spherules resembling 
colloid, which stain intensely with nuclear stains and are known as Irra- 
tohyaJin (AYaldeyer). In those areas of the skin possessing a thick horny 
layer, there is formed a sharply limited layer of such keratohyalin-con- 
taining cells; this layer is known as the stratum grauulosum. In tliose 
places where the horny layer is tliin, the stratum granulosum is imper- 
fectly developed and exhibits breaks of continuity. 

Pathological cornification may occur, in the first place, as a wide- 
spread or localized increase of the horny layer, resulting in a condition 
of liypertrophy of the horny layer of the ejndennis (see Chapter VL, § "7), 



CORNIFICATION. 



2or 



or hjperJceratosis. This phenomenon may be primary — that is, due to 
intrinsic causes inherent in the anlage of the skin (ichthyosis, lichen 
pilaris) — or may be acquired as the result of external influences, mechani- 
cal lesions, infections and inflammations (callosities, corns). Further, 
there may occur disturbances in the process of cornification of the skin, 
so that certain pathological manifestations recognizable by the naked 
eye may make their appearance, such as desquamation of the skin. Such 
changes are included under the term parakeratoses. They occur esiDCcially 
as sequelae or concomitant phenomena of infections of the epidermis, and 
of inflammations of the corium and papillary body, sometimes without 
any recognizable cause ; and in these cases either the process of cornifica- 
tion or of the formation of keratohyalin, or both, is disturbed. 

Finally, pathological cornification often occurs in regions ivhere normally 
it either does not occur at all or hut to a slight extent. In the skin the cor- 
nification may extend to the ducts of the sebaceous glands and to the 
hair-follicles (ichthyosis) or to the sweat-glands (porokeratosis). Fur- 
ther, pathological cornification occurs not infrequently in the mucous 
membrane of the mouth, giving rise to white thickenings of the epithe- 
lium or to hair-like formations (hairy tongue). Horny change may be 
observed also in the mucous membrane of the middle ear, in the mastoid 
cells, in the descending urinary passages {formation of cholesteatomata) , 
and in these places it may lead to the formation of shining white scales. 

Cornification of caricer cells is not infrequently seen, particularly in 
cancers of the skin, in which the horny scales are found usually in the 
form of round masses resembling onions or pearls. Similar horny prod- 
ucts are also found in cholesteatomata of the pia and brain. 

The pathological formation of horny substance in the mucous mem- 
branes or in tumors takes place either simj^ly through cornification of the 
cell -membranes with contraction of the cell, or it may be combined with 
the formation of keratohyalin as in the case of typical cornification. 
The formation of keratohyalin and the cornification of epithelial cells 
often occur irregularly distributed, particularly in cancers. 

According to the view of MertscMng and Ernst, the granules of keratohj-alin are 
derived from the nucleus, and represent chromatin which has escaped from the nucleus. 
In favor of this view is the fact that the nuclei lose their chromatin simultaneously with 
the appearance of the keratohyalin. 

Literature. 

Cornification. 

Best: Verhornung des Bindehautepithels. Beitr. v. Deutschmann, 34 H., 1898. 
Bostrom: Piale Epidermoide. Cbl. f. allg. Path., viii., 1897. 
Brosin : Die schwarze Haarzunge, Leipzig, 1888. 
Denoir : De la langue noire, Paris, 1878. 

Dinkier: Schwarze Haarzunge. Virch. Arch., 118 Bd., 1888. 

Ernst: Bezieh. d. Keratohy alius zum Hyalin. Virch. Arch., 130 Bd., 1892 (Lit.); 

Normale Verhornung. Arch. f. mil^r." Anat., 47 Bd., 1896; Pathol. Verhornung. 

Beitr. v. Ziegler, xxi., 1897 (Lit.). 
Haug-: Das Cholesteatom d. Mittelohrraume. Cbl. f. allg. Path., vi., 1895. 
Joseph: Porokeratosis. Arch. f. Derm., 39 Bd., 1897. 
Leloir: Leukoplakie buccale. Arch, dephys., x., 1887. 
Mertsching: Keratoliyalin u. Pigment. Virch. Arch., 116 Bd., 1889. 
Nehrkorn: Meningeale Perlgeschwulst. Beitr. v. Ziegler, xxi., 1897. 
Posner: Schleimhautverhornung. Virch. Arch., 118 Bd., 1889. 

Unna: Handb. d Hautkrankheiten, Leipzig, 1888; Die Histopathologic der Haut- 

krankheiten, Berlin, 1894; Wesen der Verhornung. Munch, med. Woch., 1896. 
Wassmuth: Hyperkeratosis diffusa. Beitr. v. Ziegler, xxvi., 1899. 



208 



THE RETROGRADE CHANGES. 



XI. Amyloid Degeneration and tiie Amyloid Concretions. 

§ 63. Amyloid degeneration is a peculiar degeneration of the con= 
nective tissue of the blood=vessels, characterized by a deposit of an 
albuininoid substance (amyloid) in the affected part, so that the tissue in- 
creases in mass and at the same time acquires a peculiar, glassy, homoge- 
neous appearance. The degeneration may occur in almost all the organs 
of the body; but is especially frequent in the spleen, liver, kidneys, in- 
testine, stomach, adrenals, pancreas, and the lymph-glands. It is more 
rarely observed in adipose tissue, thyroid gland, aorta, heart, muscles, 
ovaries, uterus, and in the urinary passages. 

Extensi^ e deposits of amyloid may be recognized by the naked eye, 
as the affected parts present a translucent appearance resembling bacon 
{Jardaceous degeneration). 

In the spleen the change occurs most frequently in the follicles, which 
in a certain stage of the degeneration may become converted into homo- 
geneous, translucent bodies (Fig. 77, I)) resembling grains of boiled sago, 
wherefore this form of amyloid spleen is know^n as sago spleen. When 
the amyloid change occurs throughout the spleen-pulp it may be recog- 
nized on the cut surface of the organ as more or less distinct spots or 
streaks. Ultimateh^ the greater part of the substance of the spleen may 
become affected. The spleen is thus enlarged, its consistency becomes 




Fig. 77.— Amyloid degeneration of the splenic follicles and neighboring tissue. (Miiller's fluid, 
tiJBraatoxylin, and eosin.) a. Transverse section of splenic artery; h, amyloid areas; c, pulp; t?, tra- 
beculte. 'x 30. 

very hard, and the organ under certain conditions may be completely 
transformed into a bacon-like substance (Jardaceous spleen). 

The liver, in cases of well-marked amyloid degeneration, is increased 
in size and of a firmer consistency. On section, the liver-tissue is found 
to be replaced to a greater or less extent by translucent, lardaceous 
masses, betw^een which the remains of the liver-tissue appear as brown- 
ish or yellowish (from abundance of contained fat) areas. 



AMYLOID. 



209 




The Udney, in cases of extensive amyloid change, is likewise enlarged 
and hardened, and on section shows hyaline, lardaceous spots and streaks 
of hrni consistency. More frequently there is found a white, fatty, 
swollen, or normal-sized kidney, in which only here and there may be 
seen small hyaline granules or streaks, or the presence of amyloid may 
be recognized only after the tissues have been treated with iodine. 

In the intestine and lymph-glands the degeneration usually cannot 
be recognized without 
the aid of the micro- 
scope and chemical re- 
agents; and the same 
thing is true in regard 
to the other organs 
which are more rarely 
affected, such as adi- 
pose tissue, heart-mus- 
cle, the great blood-ves- 
sels, the thyroid gland, 
etc. 

The substance which 
is deposited in amyloid 
degeneration forms 
chiefly shining, homo= 
geneous masses, which 
exhibit a characteristic 
reaction with iodine as 
well as icith various ani- 
line dyes. Iodine dis- 
solved in water, or bet- 
ter in a solution of 

potassium iodide, and poured over the affected tissue, stains the amyloid 
substance a dark brownish-red (mahogany brown). In thin sections, 
under the microscope, the amyloid appears bright brown-red (Fig. 78, b) 
while the remaining tissue is of a straw-yellow color (a). 

In marked amyloid degeneration, when the tissues are of a wooden 
hardness, the iodine reaction sometimes gives a blue or green color. Pre- 
parations which ha^ e been changed to a mahogany brown through the 
action of iodine become still deeper brown when treated with dilute sul- 
phuric acid or with a solution of zinc chloride, or they may become 
bright red, violet, blue, or green. This reaction is, however, imperfect 
in the majority of cases. 

Methyl violet stains amyloid a ruby red (Fig. 78, a, b), while the nor- 
mal tissue takes a blue or dark blue- violet. 

Because of the peculiar reaction with iodine, Virchow was led to re- 
gard the amyloid substance as a non-nitrogenous body closely related to 
cellulose or starch, inasmuch as cellulose when treated with iodine and 
concentrated sulphuric acid becomes bright blue, and starch similarly 
treated gives an ultramarine color. Virchow accordingly gave the name 
amyloid to the newly discovered substance. Several years later Fried- 
reich and Kekule showed that amyloid is a nitrogenous body of an albu- 
minous nature. According to the investigations of Krawkow amyloid 
is a firm combination of chondroitin-sulphuric acid with an albumin. 

The i3eculiar reactions of amyloid enable us to detect its presence in 
the tissues when it is present in such small amounts as to be otherwise 



Fig. 78.— Section from amyloid liver treated with iodine. 
livHr-rissue ; /(.amyloid areas; c. Glisson's capsule. 



n. Normal 



210 



THE RETROGRADE CHANGES. 



practically invisible. In the microscopic examination of fresh prepara- 
tions care should be taken to wash out the blood from the piece of tissue, 
since the color resulting from the combination of the blood and the iodine 
may be deceptive. 

Amyloid is very resistant to acids and alkalies. Alcohol and chromic 
acid do not affect it ; and it is also very resistant to putrefactive changes. 




Fig. 79.— Amyloid degeneration of the splenic follicles and pulp. (Alcohol, methyl violet, hydrochloric 
acid.) a, Follicle showing marked degeneration ; Z>, pulp showing beginning degeneration. X 300. 

Amyloid is deposited in the ground- substance of the connective tissue of 
the blood-vessels, especially in the walls of the small vessels. Living cells are 
not affected. In the connective tissue the amyloid substance appears 
first between the fibrillse. 

In the acini of the liver the amj^loid is found along the capillaries. 
The endothelium (Fig. 80, c) is covered on its outer side by a thick layer 
of a homogeneous, glassy substance, which in part may be broken up 
through numerous clefts into lumpj^ masses (c) of amyloid material. 
The liver-cells between the amyloid masses are either intact (a) or com- 
pressed (b), or already atrophic, or may have wholly disappeared. 
They very often contain fat. The afferent blood-vessels of the liver, 
particularly the media of the arteries, may also show amyloid deposits. 

In the kidneys (Fig. 81) the amyloid is found particularly in the 
vessel-walls. The capillaries of the glomeruli (b) may be greatly thick- 
ened and homogeneous; likewise the arteries (/), the veins, and the 
capillaries (k) of other parts of the renal parenchyma may show amyloid 
deposits. In the intestinal mucosa the deposit is also found particularly^ 
in the walls of the blood-vessels. 

In fat-tissue, Avhich is occasionally extensively involved, the amyloid 
substance is found partly in the vessel- walls, and partly in the connec- 
tive tissue, and the membranous sheath of the fat-cells may be entirely 
converted into a hyaline mass. In the spleen the connective-tissue tra- 
beculse (Fig. 79, a, b) and the vessel-walls are especially likely to be 
affected, and may suffer a marked thickening (b). In strij)ed muscle 
the perimysium internum and the sarcolemma are involved. In glandu- 
lar organs possessing a tunica propria, as, for example, the mucous 



AMYLOID. 



211 



glands and the kidneys, this niembi-aiie may become afifected and greatly 
thickened. 

The results of amyloid degeneration upon the functions and vitality 
of the affected organ are shown, through anatomical investigation, 
most prominently in the marked change of structure on the one hand, and 
on the i)ther hand in the associated degeneration and the disappearance of 
the cellular elements. Amyloid disease is eminently degenerative in 
character. The connective tissue itself is permanently changed, as the 
practically insoluble amyloid is never removed from it. 

The deposit of amyloid substance in the tissues of the blood-vessels 
leads to a very marked thickening of their walls, and to a narrowing or 
€ven obliteration of their lumina (Fig. 81, h), and in this way to a per- 
manent disturbance of circulation. The amyloid masses may compress 
neighboring epithelial structures (Fig. 80) and cause them to atrophy. 
Often there is associated a fatty degeneration of the epithelium (Fig. 81, 
€, f), particularly in the kidneys; but this change is not to be referred 
wholly to the disturbances of circulation caused by the amyloid deposit. 
It is more likely that the fatty degeneration, at least in part, is a path- 
ological process running parallel with the amyloid disease, and caused 
by the same conditions producing the latter. Consequently, in some 
cases the amyloid change may be slight, while the fatty degeneration is 
very marked. 

In the spleen and lymph-glands the lymphoid cells lying in the 
meshes of the thickened reticulum (Fig. 79) disappear as the result of 
atrophy and fatty degeneration. In muscles the contractile substance 




Fig. 80.— Amyloid degeneration of the liver. (Alcohol, Van Gieson's.) a. Liver-cells, in part containing 
fat : t», compressed liver-cells ; c, amyloid. X 

diminishes in proportion to the increase of the amyloid deposit in con- 
nective tissue. 

Amyloid deposit is usually a sequela of cachexia due to chronic ulcer- 
ative tuberculosis of different organs, chronic suppuration (for example, of 
the bones), syphilis, or chronic dysentery. In the cachexia of carcinoma 



212 



THE RETROGRADE CHANGES. 



it is but rarely observed. In rare cases the degeneration occurs without 
being associated with any of the above-mentioned diseases. 

According to investigations by Czerny, Krawkow, Lubarsch, David- 
sohn, Maxiniow, Nowak, Petrone, and Schepilewsky amyloid may be 
produced experimentally in the spleen, liver, kidneys, and intestines of 
various animals, rabbits, chickens, doves, mice, and dogs, through the 
production of suppurations lasting several weeks. Suppurative processes 
caused by staphylococci and oil of turpentine appear in particular to 
favor the formation of amyloid. In a number of cases amyloid was also 
successfully produced through injections of decomposed bouillon, dead 
cultures of staphylococci, rennet-ferment, and pancreatin (Schepilew- 
sky), when the inflammation produced by these agencies ran a somewhat 




' h 



Fig. 81.— Section of an amyloid kidney. (Miiller's fluid, osmic acid, methyl violet.) a, Normal vascu- 
lar loops ; amyloid vascular loops ; c, fatly glomerular epithelium ; c,, fatty capsular epithelium ; c/, fat- 
drops lying against the outer surface of the capillary walls ; c, fatty epithelium in situ ; /, desquamated 
and fatty epithelium ; g, hyaline coagula (cast); transverse section of a cast composed of fat-drops : i, 
amyloid artery ; ^, amyloid capillary ; I, cellular infiltration of the connective tissue ; m, round cells within 
the tubules. X 300. 

chronic course. Krawkow observed the beginning of amyloid formation 
after three days, Nowak after eight days. 

The origin of the amyloid substance has not yet been definitely deter- • 
mined. The results of experimental investigation vary greatly, tlie de- 
generation being often absent in cases of chronic suppuration (particu- 
larly in dogs). It is probable that the blood brings to the tissues some 
substance which is changed into amyloid at the site of deposit. It has 
been many times shown that as the antecedent of amyloid there is found 
a hyaline substance in the tissues, which does not give the amyloid reac- 
tions. Similar observations have been occasionally made in man. The 
material from which amyloid arises is formed, perhaps, by disintegrating 
pus-cells or tissue-cells at the seat of the primary disease. 

According to Krawkow, there are found normally in the artery-wall of the horse, in 
the ligamentnm nuchse of cattle, in the stroma of the spleen of calves, and in the mu- 



LOCAL AMYLOID INFILTRATIONS AND CONCRETIONS. 213 



cous membraue of the stomach, combinations of chondroitin-sulphuric acid which are 
closely related to amyloid. 

Literature. 

(Ainylokl.) 

Abraham: Ueber eigenthllmliche Formen amvloider Eutartung. Inaug.-Diss., Frei- 
burg. 1891. 

Burchardt: Amyloidfiirbuug (Gentiauaviolett, Salzsaure). Yirch. Arch., 117 Bd., 
1889. 

Czerny: Zur Kenutn. d. glykogenen ii. amyloiden Entartung. Arch. f. exp. Path., 
31 Bd., 1893. 

Davidshon; Exper. Erzeiigung von Amyloid. Yirch. Arch., 150 Bd., 1897; Erken- 
nung zweier Stadien der Amyloidentartung, ibid., 155 Bd., 1899, 

Eberth: Die amyloide Entartung. Virch. Arch., 80 Bd., 1880. 

Friedreich, u. Kekule: Zur Amyloidfrage. Virch. Arch., 16 Bd., 1859. 

Grandis et Carbonne: Reaction de la substance amyloide. Arch. ital. de biol., xiv., 
1891. 

Grig-orieff: Resorptionsfahigkeit d. Amyloids. Beitr. v. Ziegler, xviii., 1895. 
Henning's: Zur Statistik u. Aetiologie der amyloiden Entartung. Inaug.-Diss., Ber- 
lin, 1880. 

Hjelman: Studier ofver Amyloidin jurens. Inaug.-Diss., Helsingfors, ref. Cbl. f. 

allg. Path., ii., 1891. 
Jiirg-ens: Eine neue Reaction auf Amyloidkorper. Yirch. Arch., 65 Bd., 1875. 
Krawkow: Exper. Erzeug. v. Amyloid. Cbl. f. allg. Path., 1895; Arch, de med. 

exp., 1896; Chemie der Amyloidsubstanz. Arch. f. exp. Path., 40 Bd., 1897. 
Kiihne u. Rudnew: Zur Chemie der amyloiden Entartung. Yirch. Arch., 33 Bd., 

1865. 

Kyber: Die amyloide Degeneration, Dorpat, 1871; Yirch. Arch., 81 Bd., 1880. 
Xievene: (Chondroidin-sulphuric Acid) , ^led. Rec, 1900. 

liindemann : Jodschwefelsaurereaction u. Amyloid (Krystalle). Cbl. f. allg. Path., 
1897. 

Lubarsch: Exper. Erzeugung von Amyloid. Yirch. Arch., 150 Bd., 1897; IT3'aline 
u. amyloide Degen. Ergebn. d. allg. Path., iv., AYiesbaden, 1899. 

Maximow: Experimentell hervorger. Amyloidentartung. Yirch. Arch., 153 Bd., 
1898. 

ITeumann. Ueber Amyioiddegeneration des Fettgewebes. Centralbl. f. allg. Path., 
i., 1890. 

Nowak: Aetiologie der Amyloidosis. Yirch. Arch., 152 Bd., 1898. 
Petrone: Degen. amyloide experimentale. Arch, de med. exp., 1898. 
Rabe: Amyloidentartung bei Thieren. Jahresber. d. K. Thierarzneischule z. Han- 
nover, 1883-84. 

Schepilewsky : Exper. Erzeugung amyloider Degeneration. Cbl. f. Bakt., xxv., 1899. 
Tschermak: Steliung d. amyloid. Subst. Zeitschr. f. plws. Cliem., xx., 1875. 
Virchow: Ueber eine im Gehirn und Riickenmark des Menschen aufgefundene Sub- 

stanz mit der chemischen Reaction der Cellulose. Yir. Arch., 6 Bd., 1854. 
Wichmann: Die Amyloidentartung. Beitr. v. Ziegler, xiii., 1893. 
Zieg-ler: Amyloide Tumorbildung in der Zunge und im Kehlkopf. Yirch. Arch., 65 

Bd., 1875. 

§ 64. The form of amyloid degeneration just considered is a disease, 
which usually api3ears as a multiple affection of several organs, or, if 
confined to a single organ, appears as a diffuse change extending through- 
out the whole organ. There is, however, a localized form of amyloid 
deposit, appearing either as a local amyloid infiltration of the tissues or in the 
form of free concretions. 

The local amyloid infiltrations occur in part in very cellular granu- 
lations (conjunctiva) and in tissues showing chronic inflammatory proc- 
esses; and in part in scars and in hyperplastic proliferations of connec- 
tive tissue. They are also found occasionally in tumors in which other 
retrograde changes have begun. In certain cases only small deposits are 
found in the affected tissues, usually in the vessel -walls. In other cases 



214 



THE RETROGRADE CHANGES. 





larger nodules consisting almost wholly of amyloid may be formed, and 
these may acquire a wooden hardness. 

Here also the amyloid substance is deposited in tlie ground-substance of the 
tissue ^ but it has beeu claimed by some authors (Eiihlmann) that the 
cells of the tissue may acquire a hyaline appearance and give the amy- 
loid reactions. 

Such local formations of amyloid have been found in the inflamed 
conjunctiva, in syphilitic scars of the liver, tongue, and larynx, in in- 
flamed lymph-glands, ulcers of bone, and in tumors of the larynx and 
stomach. Tumor -like nodides of amyloid also occur in the conjunctiva, 
tongue, larynx, and trachea under conditions in which it is impossible 
to establish any relationship between them and inflammatory processes, 
and where besides the hyaline masses there is but little normal connec- 
tive tissue present. According to Manasse such tumors may arise also 
from sarcoma-like proliferations. 

Free amyloid concretions or corpora amylacea occur most frequently 
in the tissues of the central nei vous system, especially in the substance 
of the spinal cord, and in the ependyma of the ventricle. They are 

found also in the prostate. In the 
nervous system they appear as 
small (Fig. 82, c), dull-shining, 
mostly homogeneous bodies, more 
rarely consisting of a nucleus and 
an outer shell (Eedlich) ; in the 
prostate they form larger (Fig. 82, 
a) bodies which usually show a dis- 
tinct stratification. Corpora amy- 
lacea have also been found in car- 
cinomata (Wagner, Langhans), and 
have been repeatedly observed in 
the lung (Friedreich, Zahn, Zieg- 
ler), where they occur in inflam- 
matory areas, h^emorrhagic extra- 
vasations (/>), and in emphysema. 

The local deposits of amyloid and 
the free amyloid concretions cannot he 
regarded as being wholly of the same 
nature as the progressive amyloid de- 
generation of connective tissue. Some 
of them indeed give characteristic amyloid reactions, and the corpora 
amylacea of the nervous system, in particular, become blue when treated 
with iodine and sulphuric acid. But, in the case of these bodies, we 
have to do with formations which are dependent essentially upon local 
conditions for their origin ; and which are derived in part from epithe- 
lium, and in part from connective- tissue cells. They are, therefore, to 
be regarded partly as modified epithelial hyalin (§ 61), and partly as 
modified connective-tissue hyalin (§ 66). The prostatic concretions are 
formed through the fusion of masses of degenerating epithelial cells or 
of fragments of the same (epithelial colloid, § 61) ; and the similar bodies 
found in the lungs and in tumors are composed essentially of the pro- 
ducts of disintegrated cells, though in part also of albumin derived from 
the blood. Eedlich considers the corpora amylacea of the nervous sys- 
tem, which stain deeply with hsematoxylin, to be derived from the nuclei 
of the neuroglia-cells, and to represent a senile retrograde change of 



Fig. Corpora amylacea. a. Laminated pros- 
tatic concretions. X 300. Corpus amylaceum 
from an old haemorrhagic infarct of the lung, with 
haematoidin crystals in its nucleus. X 200, c. 
Corpora amylacea from the spinal cord. X 400. 



HYALIN. 



215 



the tissue. On the other hand, according to Stroebe, they are formed 
from fragments of swollen axis-cylinders, while by Siegert they are be- 
lieved to be of cellular origin. 

Literature. 

(^Local Formation of Amyloid and Amyloid Concretions. ) 

Burow: (Larynxtumoren. ) v. Langenbeck's Archiv, xviii., 1867. 

Ceci: Corpusculi amilacei dell' eucefalo e midollo spinale. Atti de Lincei, ix., 1881. 

Eiger: Zur Amyloidfrage. Cbl. f. allg. Path., xi., 1900. 

Friedreich: Corpora amylacea in den Lungen. Vircli. Arch., 9, 10 Bd., 1856. 
Fumagalli e Krach: Degeu. amiloidedella congiuntlva. Arch, per le Sc. Med., xix.» 
18y5. 

Glockner; Tumorformiges Amyloid d. Larynx. Virch. Arch., 160 Bd., 1900. 
Grawitz-. (Nase imd Luftrohre des Pferdes.) Yirch. Arch., 94 Bd., 1883. 
Hildebrand: Corpora amylacea in einem endostalen Sarkom. Virch, Arch,, 140 Bd., 
1895. 

Hippel: (Augenlid.) Arch. f. Ophthalm., 25 Bd. 

Kraus: (2kinge, Augenlid, Trachea, Leber.) Zeitschr. f. Heilk., vi., 1885; vii., 1886. 
Langhans: Corpora amylacea der Lunge. Virch. Arch., 38 Bd., 1867. 
Leber : (Augenlid). Arch. f. Ophthalm., xix. and xxv. 

Manasse: Tumorformiges Amyloid des Larynx. Virch. Arch., 159 Bd., 1900, 
Posner: Ueber Prostataconcretionen, Zeitsch. f. klin. Med., 16 Bd., 1889. 
Rahlmann : (Augenlid.) Arch. f. Augenheilk., x. ; Virch. Arch., 87 Bd., 1882. 
Redlich: Die Amyloidkorperchen des Nervensystems. .Tahrb. f. Psych., x., 1891. 
Rumschewitsch •, Hyaline u. amyloide Entartung d. Bindehaut. Arch. f. Augenh.,, 
25 Bd., 1892. 

Schmidt: Amyloidtumoren d. Zunge. Virch. Arch., 143 Bd., 1896. 
Sieg-ert: Unters. lib. d. Corp. amylacea. Virch. Arch., 129 Bd., 1892. 
Stilling; Entstehung von Concrementen der Prostata. Virch. Arch., 98 Bd., 1884. 
Stratz; Amyl. Degen. e. Uteruspolypen. Zeitschr. 1". Gebh., xvi., 1889. 
Stroebe: Reparat. Vorgange bei Heilung von Rilckenmarkswunden. Beitr. v. Zieg- 
ler, XV., 1894. 

Vossius: Amyloide Degeneration der Conjunctiva. Beitr. v. Ziegler, iv., 1889. 
Zahn- Corpora amyloidea der Lung \ Virch. Arch., 72 Bd., 1878. 
Ziegler: Amyloide Tumoren der Zunge und des Kehlkopfs. Virch. Arch., 65 Bd., 
1875. 

XII. Hyaline Degeneration of Connective Tissue and the Hyaline 
Products of Connective=tissue Cells. 

§ 65. Under the head of hyaline degeneration of connective tissue 

may be grouped those changes in which the fibrous ground- substance of the 
connective tissue of the blood-vessels acquires a hyaline character without giving 
the specific reactions of amyloid (Fig. 83). The change may involve nor- 
mal connective tissue (Fig. 83), or that altered by inflammation, as well 
as the newly formed connective tissue of inflammatory new-growths and 
of tumors. It is dependent partly ui)on local and partly upon general 
disturbances of circulation. Hyaline degeneration is found most often 
in the connective tissue of the thyroid (Fig. 83, b) ; the valvular endo- 
cardium ; intima of the arteries ; the entire wall of the smaller vessels, 
particularly of the brain and spinal cord ; the lymph-glands (Fig. 85, a, 
b) ; glomeruli of the kidney ; the connective tissue and blood-vessels of 
connective tissue tumors of the dura mater (psammoma), parotid, and 
submaxillary glands (angiosarcoma) ; the connective tissue of corneal 
scars; the peripheral portions of tuberculous nodules; the connective 
tissue of tuberculous tend on -sheaths and bursse mucosae (Fig. 84, b). 
Hyaline degeneration of connective tissue possesses no specific staining 



216 



THE RETROGRADE CHANGES. 



reactions, as does amyloid. Staining with Tan Gieson's (acid fuchsin 
and picric acid) gives to liyalin in the great majority of cases an intense 

fnchsin red ; bnt this re- 
action is sometimes want- 
ing. It is pi'obable tliat 
the degeneration of con- 
nective tissne known as 
hyaline represents a va- 
riety of degenerative con- 
ditions. By many anthoi's 
hyaline coagnla of exu- 
dates, occurring in the 
tissues, are included in 
this group. 

In many cases (thick- 
ening of the heart-valves 
or of the intima of ar- 
teries) the tissue appears 
on microscopical examin- 
ation to be very thick 
and dense, and from this 
fact the condition has 
been designated sclerosis. 
The cause of the thicken- 
The gradual disappearance 
67), or softening even to 




Fift. 83.— Hyaline degeneration of the connective tissue of a 
colloid goitre. (Alcohol, Van Gieson's.) ' a. Follicles containing 
colloid ; b, hyaline connective tissue; c, blood-vessel. X 3U0. 



ing and homogenous character is not known, 
of the nuclei, the subsequent calcification (see 
the point of complete disintegration (for example in sclerotic areas of 
the intima), the sequestration of the altered tissue from the normal (for 
example, in the degenerated portions of the walls of the burs?e), all point 
to the fact that the process is essentially degenerative in character. 

In other cases the appearance of the hyaline tissue resembles closely 
that of amyloid degeneration, and there is associated with the hyaline 
change a pronounced increase of bulk, i^articularly so in the case of 
hyaline degeneration of the small vessels of the central nervous s^^stem, 
glomeruli, and the 
lymph-glands (Fig. 85, 
a, h)j more rarely in the 
hyaline degeneration of 
the connective tissue it- 
self. There occur, more- 
over, though very rarely, 
certain forms of hyaline 
degeneration involving 
several organs, the heart 
(Fig. 86, b, c), serous 
membranes, intestinal 
wall, etc., with the for- 
mation of glassj^ masses, 
which in i)art give the 
amyloid reaction, and in 
part do not. In prolif- 
erations of the conjunctiva there have been frequently observed hyaline 
degenerations of the reticular ground-substance with nodular thicken- 
ings of the same ; and these changes give the amyloid reaction only in 




Fig. 84.— Hyaline degeneiation of the connective tissue of the 
wall of a tuberculous bursa. (Miiller's fluid, haematoxylin, and 
eosin.) a. Fibrous connective tissue ; b, hyaline connective tissue. 
X 40. 



HYALINE DEGENERATION OP CONNECTIVE TISSUE. 217 



part. It may therefore be assumed that there is a form of hyaliue de- 
generation of the connective tissue, which is closely related to amyloid, 
and may become changed into the latter (see § 63) ; and that it arises 




Fin. 85. Fig. 86. 

Fig. 85.— Hyaline degeneration of the blood-vessels of an atrophic axillary lymph-gland. (Alcohol, 
carmine.) a. Hyaline vessel with open lumen ; 7>, obliterated vessel. X 200. 

Fig. 86.— Hyaline degeneration of the connective tissue of the myocardium. (Alcohol, haematoxylin, 
carmine.) a. Normal connective tissue ; hyaline connective tissue ; c, hyaline masses; d, transverse 
section of normal muscle-cells, of atrophic (e). X 250. 

through the deposit of a hyaline insoluble albuminous body which is 
j)robably derived from the blood. 

The preparation shown in Fig. 86 was taken from the heart of a woman of fifty- 
five years of age, the greater part of the heart-wall presenting a hyaline degeneration. 
In both endo- and pericardium there were numerous hyaline nodules and flattened 
masses. The muscle tissue was in part degenerated, as shown in the figure. Associ- 
ated with this condition there was extensive degeneration of the blood-vessels, par- 
ticularly of the intestines, tongue, lungs, heart, and urinary bladder. The peritoneum 
was also thickly covered with hyaline nodules. The fact that the small areas and the 
periphery of the larger ones gave no iodine-reaction, while the central portions of the 
larger areas did so, appears to point conclusively to a close relationship between hyaline 
degeneration and amyloid. This is further supported by the fact that amyloid organs 
occasionally contain areas of hyaline degeneration which give no iodine reaction. 



Literature. 

{Hyaline Degeneration of Connective Tissue. ) 

Alzheimer: Kolloidentartung des Gehirns. Arch. f. Psych., xxx., 1898. 
Arndt: Entartung der Hirngefasse. Virch. Arch., 41 Bd., 1867. 

Best : Ueber die regressi ven Ernahriingsstorungen (hyaline Coucretionen) bei bandformi- 

ger Hornhauttrlibung, Hamburg, 1900. 
Billroth: Beitrage zur pathol. Histologic, 1858. 

Birch-Hirschfeid : Degenerat. Processe in Hornhautnarben. Graefe's Arch., 48 Bd., 
1899. 

Epping-er: Hyaline Entartung d. Hirngefasse. Yierteljahrsschr. f. prakt. Heilk., 
Prag, 1875. 

Ernst: Hyalin u. seine Beziehungen zum Kolloid. Virch. Arch., 130 Bd., 1892. 
Grawitz: Amvl. u. hyal. Neubildung in d. Nasenschleimh. e. Pferdes. Virch. Arch., 
94 Bd., 1883. 

Holschewnikoff: Hyal. Degen. der Hirngefasse. Vii'ch. Arch., 112 Bd., 1888. 
liubarsch: Albuminose Degenerationen. Ergebn. d. allg. Path., 1895. 
Lubimoff: Kolloiddegeneration d. Hirngefasse. Arch. f. Psych., iv., 1874. 
Oeller: Hyal. Gefassdeg. im Auge (Bleivergiftung). Virch. Arch., 86 Bd., 1881. 
Rahlmann: Hyaline u. amyloide Deg. d. Conjunct. Virch. Arch., 87 Bd., 1882. 
V. Reckling-hausen: Pathologic d. Kreislaufs u. der Ernahrung, Stuttgart, 1883. 
Rumsehewitsch : Amvl. u. hvaline Degen. d. Bindehaut. Arch. f. "Augenhk., 25 
Bd., 1892. 



218 



THE RETROGRADE CHANGES, 



Stilling:: Amyloide u. hyaline Degeii. d. Milz. Virch. Arch., 103 Bd., 1886. 
Vossius: Hyaline Degeneration d. Conjunctiva. Beitr. v. Ziegler, v., 1889. 
Wieger: Hyaline Entartung der Lymphdriisen. Virch. Arch., 78 Bd., 1879. 
V. Wild: Amyloide u. hyal. Degen. d. Bindegewebes. Beitr. v. Ziegler, i., 1886. 
Ziegler: Ursachen d. Nierenschrunipfung. Deut. Arch. f. klin. Med., 2r)I3d., 1878. 

§ G6. Hyaline products of connective=tissue cells arise in the first 
place from spherical masses of flat connective-tissue cells arranged m con- 
centric layers, which, in a manner similar to the cornification of epi- 
thelial cells, become changed into a hyaline substance containiiig no nuclei. 
These formations occnr most fi'equently in the meninges, the choroid 
plexns, and the pineal gland, and in the new-growths arising in these re- 
gions. Through subsequent calcification they lead to the formation of 
laminated concretions of calcium salts (see § 67, Fig. 92). 

Another kind of hyaline formation probably owes its origin to a secre- 
tory activity of the connective-tissue cells. This may be designated 
secretory connective-tissue hyalin, but it must be noted that under this term 
there is included a variety of different formations, and that, as in the 
production of colloid, the cells as a whole may be converted into hyaline 
products. In this category may be placed first the so-called granules 
(granula) — that is, the small granules which are found in the proto- 
plasm of certain leucocytes, and also in many connective-tissue cells in 
both normal and inflamed, or otherwise altered, or proliferating tissues. 
Some of these granules are oxyphile, and stain especially with eosin, so 
that they have been designated eosinophile cells. Others stain intensely 
with basic stains, and are usually designated as mast-cells (Ehrlich). In 
both forms of cells the granules may be so numerous as to con\'ert the 
cells into granule -spheres. 

Further belong here certain granules and spherules of hyaline ap- 
pearance which stain especially intensely with f uchsin, though staining 
also with methyl violet, gentian violet, etc. ; and which are known as 
fuchsinophile bodies. They are also often called Russel's bodies from the 
fact that they were described closely by Russel, who regarded them as 
parasitic fission-fungi. In the sand-tumors of the meninges the ante- 
cedents of the calcareous granules may be represented by intracellular 
hyaline spherules. 

Fuchsinophile bodies are found both in normal and in slightly altered 
tissues (adrenals, various mucous membranes — as that of the stomach — 
in the brain, spleen, and lymxDhadenoid tissues), also in inflamed tissues 
(particularly the mucous membranes, for example, of the stomach), in- 
flammatory new-growths (po]yj)i of the stomach), and in connective- 
tissue tumors. They are partly intracellular, sometimes in great num- 
bers, and partly extracellular. They are to be regarded as cell-products, 
probably of the nature of a cell -secretion, or formed as the result of the 
disintegration of the cells. Of their genesis and their comjiosition noth- 
ing definitely is known; it is possible that they have a close relationship 
with the mast-cells. Those occurring in the brain and spinal cord are 
generally classed with the corpora amylacea (§ 6-1), even Avhen they give 
no specific iodine reaction. 

Finally, there should be considered in this connection tlie larger hya- 
line spherides and easts of tubes (changed blood-vessels) resembling epithe- 
lial colloid, which are not infrequently seen in sarcomata (see Endothe- 
lioma and Angiosarcoma), inasmuch as these formations ai^e also to be 
regarded as products either of a secretory or of a degenerative x^i'oc^'^'^ 
the part of cells. 



HYALINE PRODUCTS: CELL-GRANULES. 



219 



The significance of the granules of eosinophiie and mast-cells, as well as the neu- 
trophile granules of the leucocytes (which stain with a neutral dye obtained through a 
mixture of acid fuchsin and basic methyl green), cannot be positively stated at the 
present time. ElirlicJi, Heidenhain, and Lowit regard the granules of the leucocytes 
as secretory products of a specific metabolism of the cells in which they are found, so 
that these cells ma}" be looked upon as unicellular glands. By some writers {Broioicz, 
Baudnitz) the so-called mast-cells are regarded as degenerating-cells, others {Neumann) 
look upon them as representing a stage in the development of proliferating cells, while 
others still {EhiiicJi, Bosenheim, Korybutt-Daszkiewicz) believe that they are simply cells 
which have received an excess of nutriment. 

Arnold regards the cell-granules which may be demonstrated by means of especial 
stains in leucocytes, pus-corpuscles, bone-marrow cells, and also in other cells, not as 
granules of secretion, but as representing changed structural elements of the cells aris- 
ing out of a metamorphosis of the plasmosomes — that is, the microsomes of the cell- 
cy'toplasm (see § 81). Acidophile cells may be transformed into basophile, or the reverse 
may occur; these phenomena are to be regarded as the expression of different stages 
of development with changes in the phj^sico-chemical properties. 



The formations described in ^§ 65 and 66 as connective-tissue liyalin are undoubtedly 
pathological products, which differ from each other in so far as their mode of origin and 
their chemical composition are concerned. Since we do not yet know the nature of the 
processes leading to these hyaline formations, there is nothing to do but to group them 
according to definite points of view. 

Yon Becklinghausen gives to the term hyalin a much more comprehensive meaning 
than I do. He includes under the head of hyaline degeneration different pathological 
changes which I have placed under other heads. He defines hyalin as an albuminous 
body which stains intensely with eosin, carmine, picrocarmine, and acid fuchsin; is 
homogeneous and strongly refractive ; is but slightly changed by acids ; and in its re- 
sistance to alcohol, water, ammonia, and acids resembles amyloid, but does not give the 
iodine reaction. As hyalin he includes epithelial colloid and the hj^aline products of 
connective tissue cells, as well as hyaline degeneration of the ground substance of the 
connective tissue, also hj^aline thrombi, and the hyaline coagula of inflammatorj^ exu- 
dates, and hyaline tissue-necroses. According to this author, all these formations result 
from the fusion of the elements of neighboring cells. From their external appearance, 
all these products may be properly designated hyalin ; but the following varieties must 
be recognized: epithelial hyalin (colloid, keratohj^alin), connective-tissue hyalin (hj^aline 
degeneration of the ground-substance of connective tissue, hyaline products of cells, and 
cells which have become hyaline), hlood-hyalin (hyaline thrombi), exudative hyalin (liya- 
line coagula of exudates on mucous membranes, serous surfaces, inflamed connective 
tissue, in the urinary tubules, tubercles, etc.), and hyaline tissue-necroses. In the case 
of connective-tissue hyahn a distinction must be made between the hyalin formed as a 
secretion in the cells (closely related to epithelial colloid, in its mode of origin), and 
hyaline degeneration of the ground-substance of connective tissue. 



Literature. 

{Hyaline Products of Connective-tissue Cells and Leucoeytes ; Cell- granules.) 

Altmann: Die Elementarorganismen u. ihre Beziehungen zu den Zellen. Leipzig, 1890. 
Arnold: Ueber Granulafarbung lebender Leukocvten rmd Gewebe. Virch. Arch., 157 

Bd., 1899; 159 Bd., 1900; Farbenwechsel der Zellgranula. Cbl. f. allg. Path., 

X., 1899; Vitale Granulafarbung in Knorpelzellen, Muskelfasern, und Ganglienzel- 

len. Arch. f. mikr. Anat., 55 Bd., 1900. 
Ballowitz: Elirlich'sche granulirte Zellen bei winterschlafenden Thieren. An. Anz., 

vi., 1891; 

Browicz: Sur les celles granulif^res d'Ehrlich. Bull, de I'Acad. des sciences de 
Cracovie, 1890. 

Ehrlich: Physiol, u. Pathol, d. versch. Formen d. Leukocyten. Zeitschr. f. klin. Med., 
1., 1880; Granulirte Bindegewebszellen u. eosinophile Leukocyten. Arch. f. 
Anat., Phys. Abth., 1879; Untersuch. z. Histologic d. Blutes. Gesch. Mittheil., i., 
1891. 

Galeotti: Die Granulationen in d. Zellen. Monatsschr. f. Anat., xii., 1895. 
Goldmann: Malignes Lymphom. Cbl. f. allg. Path., iii., 1892. 
Hansemann: Hyaline Zellen in Magenpolypen. Virch. Arch., 148 Bd., 1897. 
14 



220 



THE RETROGRADE CHANGES. 



Heidenhain: Histol. u, Pbvsiol. d. Dlinndarmsclileimhaut. Pfliigei's Arch., 23 Bd. 
Sup pi., 1888. 

Klien: Kussel'sche Fuclisinkorperclien u. Altmann'sclie Granula. Bcitr. v. Ziegler,. 
xi., 1892. 

Lowit: Neubildung u. Beschaffenheit d. weissen Blutkoiperchen. Beitr. v. Ziegler, 
X., 1891. 

liubarsch.: Fuclisinkorper u. Corp. amylacea. Ergebn. d. allg. Path., 1895. 
Marwedel: Veraud. d. Knochenmarks bei eiterig. Eutzlind. Beitr. v. Ziegler, xxiii.^ 
1897. 

Neumann: Mastzellen bei path. Verand. im Gehirn. Virch. Arch., 122 Bd., 1890. 
Prus: Fuchsinophile Degeneration. Cbl. f. allg. Path., vi., 1895. 
Ranvier: Traiie technique d'histologie, Paris, 1875-1888. 
Rosenheim: Mastzellen im Nervensystem. Arch. f. Psych., 17 Bd., 1886. 
Russel: Characteristic Organism of Cancer. Brit. Med. Journ., ii., 1890. 
Saltikow: Hyaline Korper in Magenpolypen u. and. Gew, Yirch. Arch., 153 Bd., 
1898. 

Sanfelice: Experim. Erzeugung d. Russel'schen Korperchen. Cbl. f. Bakt,, xxiii.,. 
1898. 

Tettenhammer : Entstehung d. acidophilen Leukocytengranula. Anat. Anz., viii,, 
1893. 

Thorel: Hyaline Korper in Magen- u. Darmschleimhaut. Yirch. Arch., 151 Bd., 1898. 
Tonton: Russel'sche Fuchsinkorp. u. Goldmann'sche Kugelzellen. Yirch. Arch., 13^ 
Bd.,1893. 

"Wolff: Bedeutung der eosinophilen Zellen. Beitr. v. Ziegler, xxviii., 1900 (Lit.). 
See also § 65. 



XIII. Petrifaction of the Tissues and the Formation of Concretions 

and Calculi. 



§ 67. It is, on the whole, of rather frequent occurrence for firm crys- 
taUine, or amorphous, granular masses to be deposited in various parts 
of the body-tissues; and when such deposits are of such extent as to 

cause hardening of the 
. . affected tissue, the result- 

ing condition is known, 
as petrifaction, or when 
the deposit consists of 
lime-salts (particularly 
phosphates) as calcifica= 
tion. 

The deposit may 
occur, in the first place,, 
in a tissue which forms, 
an integral element of 
an organ, and which 
bears its normal relation 
to the surrounding tis- 
sues. In other cases it 
takes place in portions 
of tissue which have 
been loosened from their 
surroundings; or insol- 
uble substances which 
have become changed in- 
to a firm state ; or, final- 
ly, in foreign bodies which have entered the body from without, and 
form the centres of a process of incrustation. 

In the first case there arise petrifactions of the tissues ; in the sec- 
ond, free concretions and calculi. It is to be noted, however, that un- 




FiG. 87.— Sclerosis and calcification of a uterine artery. (Forma- 
lin, haematoxylin, and eosin.) a, Sclerotic intima ; h, c, calcification ; 
d, media, x 50. 



CALCIFICATION AND PETRIFACTION 



221 



der certain conditions free concretions may become firmly attached to 
the tissues of the organ in which they lie, by means of tissue-prolifer- 
ations extending into or surrounding them. On the other hand, a calci- 




FlG. 88. FIG. 89. 

Fig. 88.— Calcification of the media of the aorta. X 350. 

Fig. 89.— Calcified vessels in the cerebellum. (Alcohol, heematoxylin.) x 100. 



fied portion of tissue may in the course of time gradually become loosened 
from its surroundings and ultimately form a free concretion. 

The cause of tissue-petrifaction is to be found chiefly in local tissue-cliangrs, 
in that the dejjosit of lime-salts usually occurs in places where the tissue 
has already died, or is in process of degeneration and necrobiosis. It 
would seem that dying tissue, which has undergone more or less modifi- 
cation, possesses a certain attraction for the lime-salts held in solution in 
the body-fluids, and enters into close combination with them. Among 
dead or degenerating tissues which yet remain attached to their neigh- 
boring structures those which have 
undergone hyaline degeneration are 
especially subject to calcification; 
particularly the hyaline, sclerotic con- 
nective tissue 65), which either 
contains but few nuclei or none at all, 
such as is not infrequently found in 
the blood-vessel walls (Figs. 87, h, c, 
and 88), in the endocardium, in en- 
larged and degenerated thyroids, or 
in thickenings of the pleura and peri- 
cardium. Further, lime -salts are fre- 
quently deposited in degenerative 
areas in the vessel-walls, or in tumors, 
or in any other portion of the body, 
in association with fatty or hyaline 
degeneration; in degenerating carti- 
lage ; in degenerating or necrotic cells, 
as, for example, in ganglion-cells or 
kidney epithelium (von Kossa), or in 
liver-cells (in poisoning with mercuric 
chloride, lead, aloin, bismuth [Fig. 
90, d, e], copper-salts, iodine, and iodo- 
form [von Kossa] ) ; or in extensive 
areas of necrosis in inflammatory pro- 
liferations. 




Fig. 



of 



:l4 

the epithelium of 



90.— Calcification 
the kidney-tubules following sublimate poison- 
ing. (Alcohol, hgematoxylin.) Patient died 
seven days after the poisoning. a, Normal 
tubules; tubule with desquamated epithe- 
lium ; c, tubule with desquamated and necrotic 
epithelium possessing no nuclei ; d, e, tubule 
with degenerated and calcified epithelium. 
X 300. 



222 



THE RETROGRADE CHANGES. 



Ill rare cases there may occur a deposit of linie-salts in organs which 
show but slight changes — for example, in the lungs. Since in part of 
such cases there is found at the same time a more rapid absorption of 
the skeleton (senile atrophy of the bones, destruction of the bones by 
tumors), this deposit is regarded as metastatic in nature, due to the over- 
loading of the blood with lime-salts. Even under these circumstances 
the immediate cause of the calcification is local, and is dependent upon 
retrogressive changes — in the lung tissue (senile atrophy, obliteration of 
vessels, venoiTS congestion) ; and the increased absorption of the skeleton 
is but a favoring factor. According to investigations by Kockel the 
elastic lamellae of the small and medium-sized vessels in particular be- 
come calcified, but the elastic fibres and capillaries of the alveolar septa 
are also involved. 

The lime-salts are first deposited in the tissue in the form of small 
granules (Fig. 88) ; and preparations may occasionally be obtained in 
which the separate calcareous granules are yet distinctly visible. 

Through the confluence of such granules larger clumps and spherules 
are formed (Fig. 89). More frequently, however, there results a more 




Fig. 91. Fig. 92. 

Fig. 91. — Calcareous concretions, a. Concretions from an Inflamed omentum; h, calcareous masses 
from a tuberculous lymph-gland which had uadergone caseation, x 200, 

Fig. 92.— Section from a psammoma of the dura mater, with concretions. (Alcohol, picric acid, 
haematoxylin, eosin.) a. Hyaline nucleated spherule with enclosed calcareous granule ; h, calcareous con- 
cretion with hyaline non-nucleated capsule, embedded in fibrous connective tissue ; c, calcareous concre- 
tion surrounded by hyaline connective tissue ; d, calcareous spicule in connective tissue ; e, calcareous 
spicule containing three separate concretions, embedded in the connective tissue. X 175. 

homogeneous deposit, in which it is impossible longer to distinguish the 
individual granules. 

The calcification may affect both the cells (Fig. 90, d, e) and inter- 
cellular substance (Figs. 87, 88, and 89). During the process of calcifi- 
cation the degenerated tissue shows dilferent reactions toward certain 
stains from that exhibited by unchanged intercellular substance or liv- 
ing cell -protoplasm, in that the area of calcification stains a dark bluish 
violet with haematoxylin (Fig. 87, h, c, d ^ Fig. 90, d, e), and red with 
picrocarmine. This applies, however, only to deposits of carbonates and 
phosphates of lime, but not to those of calcium oxalate. According to 
von Kossa, the presence of calcification may be also demonstrated by 
means of dilute solutions of silver nitrate, a black color being produced 
during the formation of silver phosphate from the organic constituents 
Temaining in the granules of calcium phosphate. 

Calcification may affect small or large areas of tissue, causing in the 



calcification: formation of concretions. 



223 



latter case a hardening and whitish coloration of the tissue. At times 
the areas of calcMcatiou may appear as sharply circumscribed spherical 
or nodular masses (Fig. 91 and Fig. 92, a, b, c), or long spicules (Fig. 
92, d) or cactus-like formations. In this manner there are produced 
concretions lying in the tissues, and these not infrequently may be 
recognized by the naked eye. Under physiological conditions such con- 
cretions in the form of laminated calcareous spherules occur particularly 
in the pineal gland and the choroid plexus (the so-called brain-sand, acer- 
vulus cerebri). As pathological formations they are found in different 
parts of the pia and dura mater, in many tumors of the same (psammoma 
or sand-tumors, Fig. 92), also in areas of caseation (Fig. 91, b), or in 
thickened connective tissue (Fig. 91, a). The origin of these formations 
may be studied to the best advantage in the psammomata. In general 
they arise through the conversion of tissue-cells (Fig. 92, a, b, c) or 
fibrous connective tissue {d) into hyaline masses, at first containing nu- 
clei (a) but later showing none (&, e), these masses then taking up lime- 
salts. Spherical concretions arise in particular from hyaline masses of 
cellular origin (a, b, c) ; the spicules {d) from hyaline connective tissue, 
though spherical concretions may be formed also in hyaline connective 
tissue (e). The connective tissue which undergoes hyaline degeneration 
and calcification is for the chief part ordinary fibrous tissue, but the spi- 
cules of lime-salts and round concretions may be formed also in the vessel 
walls. 

Literature. 

( Calcification of Tissues, and Formation of Concretions in the Tissues. ) 

Arnold: Ban und Entvvickelung der Psammome. Virch. Arch., 52 Bd., 1871. 
Diemer: Kalkablagerung in d. Serosa des Herzens. Zeit. f. Heilk., xx., 1899. 
Ernst: Ueber Psammome. Beitr. v. Ziegler, xi., 1892. 
Friedlander: Verkalkung der Gaiiglienzelleii. Virch. Arch., 88 Bd., 1882. 
Golgi: Bau und Entwickelung der Psammome. Virch. Arch., 51 Bd., 1870. 
Gottschalk: Ueber die Einwirkung des Aloinsauf die Nieren. Inaug.-Diss., Leipzig, 
1882. 

Kaufmann: Die Sublimatintoxication, Berlin, 1888; Virch. Arch., 117 Bd., 1889. 
Kockel: Kalkiucrustation d. Lungengewebes. Dent. Arch. f. klin, Med., 64 Bd., 
1899. 

V. Kossa: Kilnstlich erzeugbare Verkalkungen, Beitr. v. Ziegler, xxix., 1901. 

Kiittner : Ein Fall von Kalkmetastase. Virch. Arch., 55 Bd., 1872. 

Leber: Conjunctivitis petrificans. v. Graefe's Arch., li., 1900. 

Leutert: Die Sublimatintoxication. Fortschr. d. Med., xiii., 1895. 

Levi: Untersuchungen uber den Bau und die Entstehung der Concretionen in Psam- 
momen der Dura mater u. der Kalkplattchen in der Arachnoidea spinalis. Inaug.- 
Diss., Freiburg, 1890. 

Litten: Der hamorrhag. Infarkt, 1879; Verkalkungen in d. Nieren. Virch. Arch., 
83 Bd., 1881. 

Mallory : Calcareous Concretions in the Brain. Journ. of Path., ii., 1894. 
Meyer: Structur imd Entstehung der Sandkorper. Virch. Arch., 143 Bd., 1896. 
Neuberger: Ueber die Wirkung des Sublimates auf die Niere. Beitr. v. Ziegler, vi., 

1889; Ueber Kalkablagerung in den Nieren. Arch. f. exp. Path., 27 Bd., 1890. 
Paltauf: Ueber Phosphorvergiftung. Wien. idin. Woch., 1888. 
Rey : Ausscheidung u. Resorption des Kalks. Arch. f. exp. Path., 35 Bd., 1895. 
Ricker: Verkalkung und Steinbildung. Ergebn. d. allg. Path., iii., 1897. 
Roth: Verkalkung der Purkinje'schen Zellen. Virch. Arch., 53 Bd., 1879. 
Saikowsky: Veranderungen im Organismus durch Quecksilber. Virch. Arch., 37 

Bd., 1866. 

Schujeninoff: Muskelverkalkung. Zeit. f. Heilk., xviii., 1897. 

Steudener: Zur Kenntniss der Sandgeschwulste. Virch. Arch., 50 Bd., 1870. 

Virchow: Kalkmetastasen. Virch. Arch., 8 u. 9 Bd. ; Die krankhaften Geschwillste, 
ii., Berlin, 1865; Verkalkung abgestorbener Gehirnzellen. Virch. Arch., 50 Bd., 
1870; Cyanquecksilbervergiftung. Munch, med. Woch., 1888. 



224 



THE RETROGRADE CHANGES. 



Werra: Folgen d. voriibergeb. ii. dauernd. Yerschlusses d. Nierenarterie. Virch. 
Arch., 88 Bd., 1882. 

Zanda: EDtwickeluiig der Osteome der Aracliu. spinalis. Beitr. v. Ziegler, v., 1889. 
Sec also § 69. 

§ 68. The more common petrifactions consist of deposits of phosphate 
of lime, sometimes of carbonate ; with these some magnesium salts m-cxy 
be mixed. Under especial conditions there occur also deposits of uric= 




Fig. 93.— Deposits of urates in the knee-joint, in a case of gout, a, Condyles of the femur ; b, urate 
deposits on the cartilage. Two-thirds natural size. 

acid salts ; particularly in the disease known as gout, which is a chronic 
disturbance of the general nutrition characterized by a uric-acid diathesis 
leading to a deposit of uric acid in the tissues. 

Gout is usually inherited, and but rarely acquired; it occurs most 
frequently in certain regions, as, for example, in England and in i^'orth 
Germanj^ ; and is very rare in other countries, as in South Germany. Of 
the ultimate cause of the disease we have as yet no positive knowledge. 
It is characterized chiefly by the deposit in the body of uric-acid salts, 
chiefly sodium urate, with which small quantities of carbonate and phos- 
phate of lime are sometimes associated (Fig. 93, b). The deposit of 
these salts takes place usually during acute, tyi)ical paroxysms charac- 
terized by pain and inflammation, but very great departures from a 
typical course may occur. The deposits are found in the kidneys, skin, 

subcutaneous tissue, tendon 
-^^fm^, sheaths, tendons, ligaments, 
bursie, and articular cartilages 
(Fig. 93), but may finally be 
\r ^ , / : present in almost all the organs. 

• ' ' f ; , < ? , The metatarsoj)halangeal joint 

0 1 ' ^ ,y. ' 7 --'i of the great toe is a favorite site 
I 1 ^ " . 5 ^ * of deposit, and often the first 

!J , ^ f 9 v- ^ ^ part affected. The deposits con- 

sist essentiallv of clusters of fine 

Fig. 94.— Deposits of needle-shaped crystals of sodium olp^/lpr npprllac: rTio- Q-L^i in 
urate in the articular cartilage. (After Lancereaux.) Mt;iiut;i utjt;uiti& (^r i^. v-±j, iix 

whose neighborhood the tissues 
are degenerated or necrotic ; and 
from this it may be assumed that the urates entering the tissues in solu- 
tion give rise to the necrotic changes in the latter. 



GOUT. 



225 



The areas of necrosis and incrustation are at first of small size, but 
occasion inflammation and tissue-proliferations in their neighborhood. 
Later, with the occurrence of 
other x^^^'i'oxj'sms the deposits 
become larger, so that large 
nodules (the so-called tophi) 
are formed. These consist of 
white, plaster-like masses, and 
under certain conditions may 
form marked nodular thick- 
enings in the joints and ten- 
dons (Fig. 95). 

In the joints the articular 
cartilages at first appear as 
if sprinkled over with plaster- 
of-Paris (Fig. 93, h), but later 
the white masses penetrate 
deeper and maj^ j)ermeate the 
entire articular cartilage. In 
the kidneys the tissue-necrosis 
caused by the uric acid, and 
the resulting inflammation 
may lead to contraction and 
induration of the organ. The 
deposit affects chiefly the 
medullary pyramids, but is 
found also in the cortex. 

According to Garrod and 
Ebstein the acute paroxysms 
in gout depend upon an ex- 
cessive accumulation of uric 
acid, either as the result of 
deficient excretion by the kid- 
neys (Garrod) or of local 
changes (Ebstein). Accord- 
ing to Pfeiffer the gouty pre- 
disposition is due essentially 

to the fact that the uric acid ^^Cf- 95.— Gouty nodes of the hand. (After Lancereaux.) 

in the body-fluids is produced 

in a form which is soluble with difficulty, and tends to be deposited in 
the tissues where it may collect in such quantity as to cause a localized 
necrosis. The symptoms of the gouty paroxysm are supposed to depend 
upon an increased alkalinity of the body -fluids caused by especial con- 
ditions, as a result of which there follows a partial solution of the de- 
posited uric acid, in the course of which process attacks of pain and 
symptoms of inflammation are produced. On the other hand, von 
Noorden regards the formation and deposit of uric acid as a secondary 
process, due to the local action of a special ferment, and quite inde- 
pendent of the amount and condition of the uric acid in other parts of 
the body. 




226 



THE RETROGRADE CHANGES. 



Literature. 

{Gout and Gouty Deposits.) 

Aschoff: Exper. Harusaureablagemngen. Verb. d. pathol. Gesell., ii., Berlin, 1900. 
Berkart: Path, of the Gouty Paroxysm. Brit. Med. Journ., 1., 1895. 
Cantani: Specielle Pathol, u. Ther. der Stotfwechselkrankheiten, ii., Berlin, 1880. 
Charcot: Maladies des vieillards, goute et rheumatismes. (Euvres compl., vii., 
Paris, 1890. 

Duckworth.: Traite de la goutte, Paris, 1893; Die Gicht, Leipzig, 1894. 

Ebstein: Die Natur u. Behandlung d. Gicht, Wiesbaden, 1882; Verhandl. d. YIII. 

Congr. f. inn. Med., W iesbaden, 1889; Beitr. z. Lelire v. d. harusaureu Diathese, 

Wiesbaden, 1891. 

Ebstein n. Sprague: Beitr. z. Analyse gichtischer Tophi. Yirch. Arch., 125 Bd., 
1891. 

Freudweiler: Exp. Unters. iiber das Wesen d. Gicht. Deut. Arch. f. klin. Med., 63 
Bd., 1900. 

Garrod: Die Natiir und die Behandlung der Gicht, Wurzburg, 1861. 

His: Wirkung des sauren harns. Natrons. Deut. Arch. f. klin. Med., 67 Bd., 1900. 

Kolisch: Wesen und Behandlung der uratischen Diathese, Stuttgart, 1895. 

Kionka: Vogelgiclit. Arch. f. exp. Path., 44 Bd., 1900. 

Levison: Die harnsaure Diathese, Berlin, 1893. 

Likhatscheff : Uratablagerung nacli Ureterunterbindung. Beitr. v. Ziegler, xx., 1896, 
Minkowski: Phys. u. Pathol, d. Harnsaure. Arch. f. exp. Path., 41 Bd., 1898. 
Mordhorst: Entstehung der Uratablageruugen. Virch. Arch., 148 Bd., 1897. 
V. Noorden: Pathologic des Stoffwechsels, Berlin, 1893. 
Pfeiffer: Das Wesen der Gicht, Wiesbaden, 1891. 
Riess: Gicht. Eulenburg's Realencyklop., 1895. 

§ 69. Free concretions are formed in the first place in the various 
ducts and cavities of the body which are lined by epithelium, as iu the 
intestines, in the ducts of the glands pouring their secretions into the in- 
testine, in the gall-bladder, urinary passages, and respiratory tract. In 
a certain sense the concretions formed in the blood-vessels and serous 

cavities might also be included in 
this group, although they are for 
the greater part firmly united to 
the surrounding tissues. 

All free concretions 2>ossess an 
organic base or nucleus. Thus en- 
teroliths Avhich form in the intes- 
tines have a nucleus of inspissated 
faeces, or foreign bodies which 
have been sv/allowed, such as hairs 
(hezoar stones or cegagropilce), or 
indigestible portions of vegetable 
food, etc., in and about wl'ich 
phosphates (ammonium - magne- 
sium phosphate and calcium phos- 
phate), and carbonates are deposited in varying proportions according 
to the nature of the food ingested. In the mouth-cavity incrustations of 
the teeth, known as dental calculi or tartar, are formed by the deposit of 
lime-salts in masses consisting of mucus, cell-detritus, and bacteria. In 
the same way there are formed in the ducts of the salivary glands and pan- 
creas oval or spherical faceted, or irregularly nodular, glandiform concre- 
tions, through the calcareous impregnation of a substance derived from 
the epithelium of the gland. 

Bronchial calculi are formed by the calcification of thickened bronchial 




THE FORMATION OF CONCRETIONS. 



227 



secretion ; the stones found in veins and arteries (phleboliths and arterio- 
liths) from the calcilication of thrombi; prostatic calculi through the cal- 
citication of the so-called amyloid concretions ; navel stoyies through the 
retention and incrustation 

of desquamated epithelium, ^^^^ 

hairs, and other substances 
which may enter the na\ el- 
depression. 

The biliary calculi and 
gall-stones found in the bile 
passages and gall-bladder are 
in part small granules, and 
partly larger spherical, oval, 
or faceted stones (Fig. 96), 
which on fracture appear 
to consist purely of crystal- 
line masses. By the em- 
ployment of proper methods 
it may be shown that these 
stones also possess a nitro- 
genous ground-substance. 

According to their essen- 
tial composition gall-stones may be classed as cholesterin, cholesterin- 
pigment, bilirubin, biliverdin -calcium, and calcium carbonate stones. 
The first two varieties are the most common ; they present a rayed, crys- 
talline, often laminated fracture ; and vary in color and in their mottling 
according to the amount of bile-pigment present. When no x:)igment is 

present they mav be color- 

y^. 



Fig. 97. 



-Section through a small < ho 
removal of the cholesterin. 



.e^l^/l■iu stuue after 
X 13. 



fi^ n 



0K\ 



W -9 



less and translucent. 

If the cholesterin be dis- 
solved out of a cholesterin 
stone by some suitable 
method, it will be found 
that the form of the stone 
is preserved, and a delicate, 
for the greater part yellow- 
ish, mass remains. This, 
when carefully embedded 
and cut into sections, is 
found under the microscope 
to consist of a delicate, ho- 
mogeneous substance (Fig. 
97) which shows concentric 
stratification and radiating 
clefts or spaces which were 
formerly occupied by the 
crystalline masses. A sim- 
ilar ground-substance may 
be demonstrated in other 
calculi after solution of 
their calcium salts. 
There can, therefore, be no doubt that gall-stones are also the result 
of the incrustation of an organic substratum, which is in all probability 
derived from the mucous membrane of the biliary ]3assages and the gall- 



Fig. 98.— Uric-acid infarct of the new-born. (Alcohol, haema- 
toxyhn. Drawn from a preparation that had been washed in 
water.) Transverse section through the pvramid of the kidnev. 
a. Transverse section of unchansred collecting tubule from the 
papilla ; Ij, dilated collecting tubule filled with uric-acid con- 
cretions ; c, remains of concretions after washing with water. 
X 200. 



228 



THE RETROGRADE CHANGES. 



bladder. Gall-stones occur especially in advanced years; stagnation of 
the bile favors their formation. Inllaniniations of the mucous membranes 
of the bile-passages (angiocholitis) lead to desquamation and destruction 
of the epithelium (eventually also to escape of leucocj^tes), and in the 
products derived from these pathological changes bilirubin and choles- 
teriu are dei^osited. When once a concretion is formed it increases in 
size through the deposit of new products of cell-disintegration which be- 
come encrusted with cholesterin, pigment, and calcium. According to 
Naunyn the originally soft nucleus of the concretion undergoes a change, 
in that it separates into firm, granular masses of pigment-calcium and 
crystals of cholesterin which are deposited upon the outer ci'ust, and into 
fluid, so that the stones may at times contain a cavity filled with fluid. 
In the course of time this cavity may again be filled with cholesterin ; 
and also the pigment and calcium in the remaining portions of the stone 




FIG. 99. FIG. lUO. 



Fig. 99.- Coral-shaped stone from tbe bladder, composed of calcium oxalate and phosphate. Natural 

size. 

Fig. 100.— Transverse section of two stones fi'om the bladder, closely fltted together, and consisting of 
sodium urate and ammonium-magnesium phosphate. Natural size. 



may be gradually replaced hj cholesterin. Further, calcium carbonate 
may also be deposited. 

The cholesterin masses from which the concretions are formed are 
derived chiefly from the disintegration of epithelial cells; likewise, the 
lime- salts combining with bilirubin are also furnished by the mucous 
membrane. 

As Ebstein has shown, the urinary caJculi, gravel, and stones are also 
composed of an organic ground-substance, an albuminous stroma, in 
which the various constituents of the urine may become deposited. Ac- 
cording to location we may distinguish calculi of the kidney and those of 
the descending urinary passages. In the kidneys the deposits may form 
only small granules lying in the tissue itself, or in part also free in the 
lumen of the urinary tubules, in the latter place lying in the products 
derived from the disintegration of necrotic epithelial cells. This is true 
in the first place of the calcifications which, as mentioned above, occur in 
the necrosed renal epithelium after poisoning with corrosive sublimate, 
bismuth, aloin, copper-salts, iodine, phosphorus, potassium chromate, 
and oxalic acid. The same thing is true of some of the gouty deposits. 
Finally, belongs here the so-called wic-acid infarct of the neiv-born, a con- 



THE FORMATION OF CONCRETIONS. 



229 



dition characterized by the appearance of yellowish-red stripes in the 
medullary pyramids. The condition is not infrequently seen in children 
dying during the first tive weeks after birth. The epithelium of the 
tubules is usually well preserved, but in places desquamation and disin- 
tegration of single cells may be found. The lumina of the tubules are 
tilled with very small, colorless or yellow granules of urates oniric acid, 
which at times show fine radiating lines (Fig. 98, &). On solution of 
these granules a delicate stroma remains (c). If as the result of the 
presence of the infarct further changes in the ei^ithelium of the tubules 
are produced, leading to the formation of albumi- 
nous material in the tubules, single granules may 
under certain conditions develop through accretion 
into large stones, but this occurrence is rare. 

In the pelvis of the kidney, ureters, urinary 
bladder, urethra, and under the prepuce concre- 
tions may be formed, either as sand, gravel, or 
stones. The last-named are oval or spherical, and 
may be smooth or rough and nodular, not infre- 
quently resembling a mulberry or mass of coral 
( Figs. 99 and 100). When several stones lie close- 
ly together, their surfaces may become faceted 
(Fig. 100). Those found in the kidney pelvis 
may form casts of the cavity and of the calyces. 

When examined in section, urinary calculi are 
sometimes homogeneous, at other times distinctly 
stratified (Fig. 100) or show radiating lines. Not 
infrequently there may be seen a nucleus and 
several zones of different appearances. The crys- 
talline masses lie partly in the spaces of the 
stroma, and partly in the latter itself ; and it may, 
therefore, be assumed that the stroma is a product 
of the mucosa of the urinary passages, and that 
its formation follows catarrhal inflammations or 
toxic necroses of epithelium when these lead to the 
collection of mucus or cell-detritus in the tubules. 

What substances are deposited in a given case 
in the products of the mucous membrane depends 
upon the existing conditions. When the condi- 
tions favoring stone -formation are associated with 
a uric-acid diathesis, or if the excretion of uric- 
acid salts by causing tissue-necrosis has at the 
same time produced the conditions favoring the 
development of concretions, the deposits in the 
organic ground-substance will consist chiefly of 
urates. Decomposition of the urine with forma- 
tion of ammonium-magnesium phosphates leads to the production of 
calculi consisting chiefly of this substance. Cystiu calculi may be 
formed when cystin is excreted by the kidneys, as the result of pe- 
culiar metamorphoses of albumin in the intestine, due to the action of 
bacteria (Baumann, von Udransky, Brieger). When once a stone is 
formed, the irritation which it causes upon that portion of the mucous 
membrane with which it comes in contact, as well as the decomposition 
of the retained urine, favors its further growth by accretion. Likewise, 
foreign bodies (Fig. 101), which have in any way entered the bladder 




Fig. 101. — Incrusted lead- 
pencil, 12 cm. long, taken from 
the male urinary bladder. 
Reduced rV. 



230 



THE RETROGRADE CHANGES. 



from without, may lead to the formation of calculi, tlirongli the irritation 
wliich they excite in the mucous membrane of the bkidder. 

Intestinal calculi are much more common in liorses and cattle than in man : since 
undigested vegetable material and hairs whicli have been licked otf are of frequent oc- 
currence in the intestinal canals of these animals and form the starting-point of such 
concretions. The true stones, wliich occur especially in horses, are rather hard masses 
consisting chief!}' of magnesium phosphate; tlie false stones consist of hairs and vege- 
table tibres which are more or less encrusted. Occasionally balls are found which con- 
sist almost whollj' of hair {a-gagropili or hezoar stones). In ruminating animals they are 
found chiefl}' in the rumen or reticulum ; in hogs, more frequently in the small intestine. 

According to Schuberg, the enteroliths of herbivorous animals consist chiefly of car- 
bonates; those of carnivorous, of phosphates. The composition of those found in man 
varies according to the food ingested. 

Urinary calculi are classified according to their composition as follows; 

1. Calculi composed cTeiejiy of uric acid or urates. 

Pure uric-acid calculi are usually small, yellow, reddish, or brownish in color, and 
hard. 

Stones consisting of urates are rarely pure. They are usuall}' covered on the surface 
with a coating of calcium oxalate and ammonium-magnesium phosphate. 

2. Calculi composed cliiefly of pJiosphates and C((rbonates. 

To this class belong stones composed of calcium pliosyJiate. aurmonivm-magnesium 
pliospliate, and calcium carbonate. The last two varieties are rare. All these calculi are 
white or grayish-white. The triple phosphate stones are soft and friable, the others 
hard. 

3. Stones composed of calciu/n oxalate. 

These are hard and rough, and of a brown color. 

4. Cystin calculi. 

These are soft, waxy, and of a brownish-yellow color. 

5. Xantldn calculi. 

These are cinnabar-red in color, smooth, and have an earth}' fracture. 

Ebstein and Xicolaier succeeded in experimentally producing urinary calculi by feed- 
ing animals with oxamide, an ammonium derivative of oxalic acid. The greenish-yellow 
concretions thus produced in the urinary passages of dogs and rabbits consisted essen- 
tially of oxamide ; on section they presented a concentric laminated structure showing 
radiating striations. They were found likewise to possess an albuminous stroma, which 
was derived from the necrosis and desquamation of epithelium caused by the action of 
the oxamide during excretion. ' 

Literature. 

{Free Concretions.) 

Baumann u. v. TJdransky: Ueber das Vorkommen von Diamiuen, sog. Ptomainen 
bei Cystinurie. Ber. d. Deutsch. chem. Ges., xxi. ; Zeitschr. f. phys. Chem., 1889. 

Brieger u. Stadth-ag-en : Ueber Cystinurie. Berl. klin. Woch., 1889. 

Cush.ing': (Gall-stones Lit.) Bull."^ Johns Hopkins Hosp., 1898. 

Ebstein: Die Xatur u. Behandlung der Harnsteine, Wiesbaden, 1884. 

Ebstein u. Nicolaier: Kiinstl. Darstellung von harnsauren Salzen in der Form v. 
Spharolithen. Virch. Arch., 123 Bd. ; Exper. Erzeugung von Harnsteinen, Wies- 
baden, 1891. 

Fauconneau-Defresne : Traite de raffection calculeuse du foie et du pancreas, Paris, 
1851. 

Fiirbringer: Xephrolitbiasis, Calculi renum, Nierenconcremente. Deut. med. Woch., 
1890. 

V. Genersich: Harte der Concremente. Virch. Arch., 131 Bd., 1893. 
Hahn: Nabelconcremente. Beitr. v. Bruns, xxvi., 1900 (Lit.). 
Leube: Darmsteine. Ziemssen's Handb. , vh. 

Lewis and Simon: Cystinuria with Diaminuria. Amer. Journ. of Med. Sc., 1902. 
Mayer: Gallensteinbirdung. Virch. Arch., 136 Bd., 1895. 

Mester: Beitr. z. Kenntniss der Cystinurie. Zeitschr. f. phys. Chem., xiv., 1889. 
Moreigne: La cystinurie. Arch, de med. exp., xi.. 1899. 

Naunyn: Die Gallensteinkrankheiten. Verb. d. X. Cougr. f. inn. Med., Wiesbaden, 

1S91; Klinik der Cholelithiasis. Leipzig. 1892. 
Posner: Studien liber Steinbilduug. Zeitschr. f. klin. Med., ix. and xvi. 



THE PATHOLOGICAL FORMATION OF PIGMENT. 



231 



Ribbert: Patb. Anat. d. Wurmfortsatzes (Bildung v. Kotlisteineu). Yircli. Arch., 
13'2 Bd., 1893. 

Schuberg-: Ban u. cliem. Zusainmensetzung v. Kothsteinen. Viicli. Arch., 90 Bd., 
1882. 

Shattock: Calculi of Calcium Oxalate from a Cvst of the Pancreas. Journ. of Path., 
iv., 1896. 

Smith: Concretions and Calculi. Ref. Ilaudb. of Med. Sc., 1901. 
Solger; Ablagerungen im Kuorpel. Arch. f. mikr. Anat., 3-1 Bd.. 1889. 
Spiegelberg-; Harusaureinfarkt d. Xeugeborenen. Arch. f. exp. Path., 41 Bd., 1899. 
Steinmann : Schaleu- und Kalksteinbildung. Ber. d. Xaturf. Ges. zu Freiburg, iv., 
1889. 

Stroebe: Arbeiten liber Bildung freier Concremente. Cbl. f. allg. Path., i., 1890 (Lit.). 
Studensky : Zur Lehre von der Bildung der Harnsteine. Deut. Zeitschr. f. Chir., vii., 
1877. 

Tross: Facettirte Speichelsteine. Beitr. v. Ziegler, viii., 1890. 



XIV. The Pathological Formation of Pigment. 

§ 70. Both connective and epithelial tissues in various parts of the 
bod}^ contain normally an autochthonous pigment, which lies icithin the 
cells, and consists either of yello\^', brown, or black granules, or forms a 
diffuse yellow or brown coloration of the cells. These autochthonous pig- 
ments are known as melanin, lipochrome, 
and hasmofuscin. In the epithelial tis- 
sues the pigment is found particularly 
in the lowest layers of the rete Malj)ighii, 
which contains pigment in all the pig- 
mented portions of the skin, also in the 
hairs, in the pigment-epithelium of the 
retina, and in many ganglion -cells. In 
the pigment-cells of the skin the granules 
are chiefly yellow and brown; in the epi- 
thelium of the retina they are black. lu 
marked iDigmentaticn of the skin other 
cells besides those of the rete Malpighii 
contain pigment. Among the connective- 
tissue cells, which most frequently con- 
tain yellow or brown pigment-granules, 
are the cells of the choroid, sclera, co- 
rium, heart-muscle, muscularis of the in- 
testine, and pia. 

The normal autochthonous pigments 
may be increased under various physiol- 
ogical and pathological conditions. For 
example, during pregnancy the pigment of 
the skin is usually more or less increased 
(chloasma uterinum), particularly in bru- 
nettes. In Addison's disease, a general 
disease leading to cachexia and which is 
dependent upon pathological conditions 
of the adrenals (see § 27), there occurs a 
decided pigmentation of the skin as a re- 
sult of an increase of the normal pigment. 
Kot infrequently spots of a bronze color 
appear in the mucous membranes of the 

inouth. Further, in atrophic conditions of the heart there is usually an 
increase of the normal heart-jngment. Yellow pigment-granules also 




Fig. 102.— Lars-e hairy pigmented mole 
over the back and hutrocks. with scattered 
spots of piprmentation over trunk and 
shoulders. (After Ruhring.) 



232 THE RETROGRADE CHANGES. 

appear in the volunifoy viusdes in conditions of atrophy; and iu old per- 
sons the smooth muM'lc of the intestine always contains more or less of a 
yellow granular pigment, so that sometimes the outer sui'face of the in- 
testine may show a j'Cllow or yellowish-brown coloration. 

The most intense grades of pathological pigmentation are met with 
in freekles, lentigines, pigmented moles (Fig. 102) and jyigmented warts, and 
in Mack melanotic tumors (see Chapter VIII.). The amount of pigment 
may be so great as to give the tissues a pure black color. 

The pigment lies for the greater part inside of tissue-cells (chromato- 
phores), more rarely in the intercellular substance. It is composed of 
yellow, brown, or black granules; not infrequently individual cells may 
be diffusely pigmented. In Addison's disease the pigment -granules are 
found partly in epithelial cells, especially in those lying directly upon 

the connective tissue (Fig. 103, 
A, a, b, and B, a), and part- 
ly iu branched connective-tis- 
sue cells (A, c, c,, d), from 
^iiich pigmented processes ex- 
tend up between the epithelial 
cells (B, c). 

In the i^igmented spots of 
the skiu and in melanotic sar- 
coiuata the pigment is partly 
contained in especially differ- 
entiated connective-tissue cells 
of large size, and partlj' in ap- 
parently normal cells of the 
given tissue, yeiy often in the 
connective-tissue cells in the 
neighborhood of the vessels 
and in the cells of the vessel- 
walls. 

In the ganglion-cells the 
pigment is composed of brown 
granules. 

The pigments just described 
are products of a specific cell- 
activity ; and we must suppose that many connective-tissue cells, gan- 
glion-cells, and muscle-cells are able to form pigment from the material 
brought to them. In the majority of cases the pigment appears to be 
formed in the places where it is found ; yet different investigations make 
it probable that the pigment may at times be transported. The pig- 
ment of the epidermis and of the hairs, at least in part, is not formed 
in the epithelial cells themselves, but in branched connective- tissue cells 
(Fig. 103 A, c, d, and B, c) which lie just beneath the rete, and send 
processes between the epithelial cells, through which the pigment is 
transferred to the latter. 

The fact that the pigment is often found particularly about the blood- 
vessels w ould seem to indicate that the material from which it is formed 
is derived from the blood, and nianj^ authors accept without question the 
view that the pigment is a derivative of the coloring-matter of the blood. 
Against this view is the fact that neither in the blood nor in the neigh- 
borhood of the blood-vessels are there present evidences of an escape of 
the red blood-cells or of a disintegration and solution of the same. It 




Fio. 103.—^, and B, Pigmented oells of the skin from 
a case of Addison's disease witli caseous tuberculosis of 
both adrenals. (Alcohol, carmine.) a. Pigmented epi- 
thelium cells from the deepest layer, in a section cut at 
right angles to the surface. A, b. Pigmented epithelial 
cells from a section made parallel to the surface. h. 
Epithelial cells containing no pigment; ccj, nucleated 
pigmented connective-tissue cells, the processes of which, 
in B, push between the epithelial cells ; d, pigmented 
cell-processes. X 350. 



THE AUTOCHTHONOUS PIGMENTS. 



233 



is, therefore, very probable that the pigment is formed either from the 
circiihiting albumin or from the albumin of the cells. 

The attempt has been made to solve this problem by means of chemi- 
cal investigations ; and the results obtained ux) to the present time favor 
the theory that the pigment is a product of cell-activity, and is formed 
from albuminous bodies. The different fonns of melanin, in which 
group the pigments of the skin and choroid are usually placed, are, ac- 
cording to the investigations of von Kencki, Sieber, Abel, Davids, aiid 
Schmiedeberg, nitrogenous bodies rich in sulphur, but vary greatly in 
composition. According to Schmiedeberg these differences depend upon 
their mode of origin, inasmuch as these pigments represent the Jinal j)rod- 
nct of a long series of metamorphoses of aJbumin ; and in their formation 
may be compared to the development of humus. The genuine albu- 
minous bodies do not furnish the material for the building up of this 
final product (Schmiedeberg), but it is derived from sulphur-containing 
bodies formed by the splitting-up of the albumins, and from which cer- 
tain carbon-containing groups have already been split off, so that there 
arise combinations which in proportion to their carbon-content are very 
rich in sulphur, and from these the melanins are formed. 

The majority of authors regard melanin as an iron-free substance. 
Erandl, Pfeiffer, Morner, and others, on the other hand, found small 
quantities of iron in melanosarcomata ; but this cannot be regarded as a 
proof that the melanin was derived from hiemoglobin, inasmuch as a 
tumor may contain besides melanin also iron-containing products arising 
from the disintegration of red blood -cells. The majority of the ]3igment 
granules give no reaction for i"on. 

Lipochrome is the term applied to the coloring-matter of adipose 
tissue, corpora lutea, ganglion-cells (Rosin), and of the greenish tumors 
known as chloromata (Krukenberg). Of the origin and nature of this 
pigment nothing definite is known. 

Hsemofuscin (von Eecklinghausen, Goebel) is the iron-free, yellow- 
ish, granular jjigment found in heart-muscle, smooth and striped muscle, 
in the cells of the glands of the stomach and intestine, in the lachry- 
mal, mucous, and sweat glands. According to von Recklinghausen this 
pigment is derived from the blood, but it has not yet been established 
that it is a hsemoglobin-derivative. The sulphur-content (Rosenfeld) 
makes it not unlikely that the haemofuscin granules belong to the mela- 
nin group. 

Aehi/ was the first to express the belief that the epithelial cells themselves do not 
form the pigment, but obtain it from wandering cells which penetrate between the in- 
dividual epithelial cells and there degenerate, the pigment and cellular debris being 
taken up by the epithelium. According to von KdlHker, "the pigment of the hair and 
epidermis is derived from pigmented connective-tissue cells which lie just beneath the 
deepest layers of the epithelium of the hair-bulbs and of the rete, and send processes 
between the delicate cells of these layers. These processes divide into long fine ramifi- 
cations which lie in the intercellular spaces and ma}' even penetrate into the cells them- 
selves, and in this way transfer their pigment to the latter." The pigment of the gan- 
glion cells and of the cells of the retina arises, on the other hand, in the ectodermal cells 
themselves. Rield and Ehrmann agree with von Kdllikev. Karg observed that, follow- 
ing the transplantation of white skin on to the surface of a leg-ulcer in a negro, the 
white grafted portions became wholly black in from twelve to fourteen weeks; and he 
concludes that, in the pigmentation of the epidermis, pigmented connective-tissue cells 
penetrate between the epithelial cells and convey pigment to the latter. Microscopical 
examination showed the presence of such pigmented processes betw^een the epithelial 
cells at a time when the latter had not yet become pigmented. Von Wild has shown 
that in melanosarcomata of the skin pigmented coniiective-tissue cells may penetrate 
between the epithelial cells. Similar pigmented connective-tissue cells are found in the 



234 



THE RETROGRADE CHANGES. 



pigmented portions of the skin or mucous membranes in cases of Addison's disease, 
usually, however, in certain areas only and not everywhere. 

Histological studies of the mode of formation of the normal pigment in vai'ious 
animals, chieiiy in fishes, amphibia, and reptiles, ha\e led to different conclusions. 
Thus Jarisch is of the opinion that the pigment of the skin and teeth of tadpoles is not 
derived from the blood, but is a product of the protoplasm, Mdiile List, on the other 
hand, believes that the pigment of the skin of fishes and amphibia is formed from 
luiemoglobin. Ehrmann holds that the melanotic pigment of all vei tebrates is a hremo- 
globin-derivative. According to Kromayer, the pigment of the skin of mammals is 
derived from the protoplasmic fibrillae (spongioplasm) and represents a degeneration- 
product of the same. 

In domesticated animals there occurs a peculiar melariosis of the internal organs, 

occasionally associated with melanosis of the subcutaneous tissue. The affected organs 
(heart, lungs, intestines, etc.) present in varying lumibers grayish or black spots, look- 
ing like ink-spots, which are produced by the deposit of pigment in connective-tissue 
cells which otherwise appear normal. 

Under the term ochronosis of cartilage, Tircltoio described a peculiar iron-free 
pigmentation of the cartilage, tendon-sheaths, and capsules of the joints, in which the 
cartilage shows a brown or black color, caused by tlie imbibition hy the ground-sub- 
stance of some pigment. Virchow believed the condition to be due to the imbibition 
of blood-pigment, and compares the process to the pigmentation of freckles and lentig- 
ines. It is probable that the condition is a more pronounced form of the hroun 'pig- 
merdation, which occurs especiall}^ often in the costal cartilage of old persons. Occa- 
sionally the pigment is deposited in a granular form, and may be found as granules 
within the cells. Of the nature of the pigment and its origin nothing is known; it 
probably belongs to the melanin group. 



Literature. 

(Autochthonous Pigments. ) 

Abel: Bemerkungen uber ihier. Melanine u. das Hamosiderin. Virch. Arch., 120 Bd., 
1890. 

Aeby : Herkunft des Pigmentes im Epithel. Cbl. f. d. med. Wiss., 1885. 
Baumel: Capsules surrenales et melanodermie, Paris, 1889. 

Bonnet: Ueber Eingeweidemelanose. Verb. d. Phys.-med. Ges. zu Wurzburg, 24 Bd., 
1890. 

Bostrom: Ueber d. Ochronose der Knorpel. Internat. Beitr., Festschr. f. Virchow, 
ii., 1891. 

Brandl u. Pfeiffer: Farbstoff melanotischer Sarkome. Zeitschr. f. Biol., 26 Bd., 1890. 
Caspary: Ueber den Ort der Bildung des Hauptpigmentes. Arch. f. Derm., xxiii., 
1891. 

Ehrmann: Physiol, u. Pathol, d. Hauptpigmentes. Viertel jahrsschr. f. Derm.. 1885, 
1886; Entwickel. u. Wauderung d. Pigmentes bei Ampliibien. Arch. f. Derm., 
xxiv., 1892; Das melanotische Pigment, Cassel, 1896; Biol. Cbl., xix., 1899. 

Goebel: Pigmentablagerung in der Darmmuskulatur. Virch. Arch., 186 Bd., 1894. 

Halpern: Ueber das Verhalten des Pigmentes in der Oberhaut. Arch. f. Derm., 

xxiii. , 1891. 

Hansemann: Ueber Ochronose. Berl. klin. Woch., 1892. 
Heile: Ochronose. Virch. Arch, 160 Ed., 1900. 

Jarisch.: Herkunft des Oberhautpigmentes. Arch. f. Derm., xxiii.; Erganzh., 1891, 

xxiv. , 1892. 

V. Kahlden: Beitr. z. path. Anat. d. Addison 'schen Krankheit. Virch. Arch., 114 
Bd., 1888. . 

Xaposi: Pathogenese der Pigmentirungen. Arch. f. Derm., xxiii., 1891. 

Karg": Ueber Hautpigment u. Ernahrung der Epidermis. Anat. Anz., ii., 1887, p. 

377: Studien iiberlransplantirte Haut. Arch. f. Anat. u. Phys., 1888. 
V. Kolliker: Woher stammt d. Pigment in d. Epidermisgebilden? Anat. Anz., ii., 

1887; Die Entstehung d. Pig. in d. Oberhautgebilden. Zeitschr. f. wiss. Zool., 

xlv., 1887. 

Kromayer: Oberhautpigment. Arch. f. mikr. Anat., 42 Bd., 1893; Zur Pigmentfrage. 
Derm. Zeit., vi., 1897. 

Krukenberg-: Grundziige der vergl. Physiol, der Farbstoffe u. d. Farben, Heidel- 
berg, 1887. 

Kunkei: Eisen in Melanomen. Sitzungsber. d. Phys.-med. Ges. zu Wurzburg, 1881. 



THE HEMATOGENOUS PIGMENTS. 



235 



List Ilerkimft d. Pigmeutes d. Oberhaut. Anat. Anz., iv., 1889, Biol. Cbl., x., 1890. 
Mackenrodt: Uiiters. liber das Chloasma uterinum. Inaug. -Diss., Halle-a.-Saale, 
188."). 

Mertsching: Studien liber Keratohyalin ii. Pigment, Virch. Arch., IIG Bd., 1889, 

Meyerson: Zur Pigmentfrage, ib., 118 Bd., 1889. 

Miura: Beitrag zur Kenntniss des Melanins, ib., 107 Bd., 1887. 

V. Nencki: Farbstoft'bilduug im thier. Korper. Correspbl. f. Schweizer Aerzte, xx., 
1890. 

V. Nencki u. Berdez. Farbstoffe der melanotischen Sarkome. Arch. f. exp. Path., 
XX., 1886. 

V. Nencki u. Sieber: Weitere Beitrage zur Kenntniss des thier, Melanins, ib., xxiv,, 
1888. 

Oppenheimer ; Pigmentbilduug in melanotischen Geschwulsten. Virch. Arch., 106 
Bd., 1886 

Pforring-er - Entstehung d. Pigmentes bei Morb. Addisonii. Cbl. f. allg. Path,, x., 
1900. 

Philippson; Ueber Hautpigment. Fortschr. d. Med., viii., 1890. 
Post: Pigmentirung der Oberhaut. Virch. Arch., 135 Bd., 1894. 
Raymond: Pigmentation dans la maladie d' Addison. Arch, de phys,, iv., 1892. 
V. Reckling-liausen : Hamochromatose. Tagebl. d, Naturforschervers., Heidelberg, 
1889. 

Rieh.1: Zur Pathologic des Morbus Addisonii. Zeitschr. f. kliu. Med., x.; Zur Kennt- 
niss der Piginentbildung im menschliclien Haar. Vierteljahrsschr, f. Derm, u. 
Syph., 1885, 

Rohring-: Pigmentnaevus. Deutsch. med. Woch., 1893. 

Rosenfeld; Das Pigment der Hamochromatose des Darms, Arch. f. exp. Path,, 48 
Bd., 1900. 

Rosin: Bail der Gauglienzellen. Deutsch. med. Woch., 1896. 

Schmiedeberg' ; Ueber die Elementarformeln einiger Eiweisskorper und liber die 
Zusammensetzung und die Natur der Melanine. Arch. f. exp. Path.. 39 Bd., 
1897. 

Senator: Ueber schwarzeu Urin u. schwarzen Ascites. Char, -Ann., xv., 1890. 
Sieber, N. : Pigmente der Chorioidea u. der Haare. Arch. f. exp. Path,, xx., 1886, 
Tietze: Beobacht. an einem Falle v. Melanosarkom mit Melanurie, Cassel, 1894. 
Virchow: Allgem. Ochronose der Knorpel u. knorpelahnlichen Theile, Virch. Arch,, 
37 Bd., 1866. 

VuiHeumier: Pigment, de la peau dans quelques cas de melanosarc. Beitr. v. Zieg- 
ler, xxiii., 1898, 

Wallach.: Beitr. z. Lelire v. d. Melanosarkomen. Virch. Arch., 119 Bd., 1890. 

V. "Wild: Einwanderung v. Pigment in d. Hautepithel bei Melanosarkom, Inaug,- 

Diss., Strassburg, 1888, 
Winkler : Ursprung des Pigmentes. Arb, a. d. embryol, Inst, in Wien, 1893, 

§ 71. Hematogenous pigments— that is, the pigments toliose origin 
from the coloring -matter of the blood mag be deynonstrated beyond miy doubt 
— are derived usually from blood which has escaped from the blood-ves 
sels, or has undergone coagulation within the vessels, and are, therefore, 
dex)endent upon local changes. In other cases they may be caused by a 
taking-up of blood-pigment into the blood or by a change in the blood 
itself, whereby granular pigment is either formed in the blood, or haemo- 
globin passes into the blood-plasma, so that pigmentation of the tissues 
results from metastatic deposits of pigment. Such pigmentations are known 
as haemachromatoses. 

Both large and small extravasates of blood very soon undergo cer- 
tain changes which are visible to the naked eye. Extravasates in the 
skin become first brown, then blue, followed by green, and finally yel- 
low. Small haemorrhages into the tissues, as in the peritoneum, pleura, 
and lungs, may show for a long time as reddish-brown spots; in de- 
comi)osing cadavers their color may be slate-colored or black. Large 
haemorrhages into the tissue, as in the brain or lungs, assume after a cer- 
tain time a rust-brown color, which later changes to an ochre-yellow, 
yellow, yellowish -brown, or brown pigmentation. All these changes of 



23() 



THE RETROGRADE CHANGES. 



color correspond to certain changes in the hemoglobin and in the iron 
which it contains. 

Whenever a hsemorrhage occnrs in the tissnes or into a bodj'-cavity, 
a certain portion of the blood-phisma and of the red hlood-ceUs may be 
taken up ?/«e/^f(»r7(^r7 throngh the lymph vessels. Another portion of the 
corpnscles gradually loses its luiemoglobin, the pale stroma of the cori)iis- 
cles remaining. The c.^icapcd hivmoglobin diffuses through the surronnding 



104 B) ; and represent a frequent residuum of hiemorrhages. A portion 
of the diffused haemoglobin may also be taken up by cells, the latter 
thereby acquiring in part a diffuse yellowish j)igiiientation, or in part 
showing the presence of yellow and brown pigment-granules. 

A third portion of the blood-corpuscles disintegrates at the site of 
the extravasation, and forms yellow and broicn granules and lumps. This 
event occurs particularly in larger extravasates in the so-called luemato- 
mata. The pigment -granules and lumps which arise either directly from 
the disintegration of red blood-corpuscles, as well as the crystals and 
granules precipitated fi'om the dissolved haemoglobin, are often taken up 
by cells, partly leucocytes and partly cells derived from proliferating 
tissue; and these form the so-called hlood-corpuscle cells 'dTi^ pigment-con- 
taining cells (Figs. 104, A and 105, «, b). 

At the beginning of the disintegration of the red corpuscles the color- 
ing-matter present is haemoglobin, but this quickly undergoes changes ; 
and the yellow and rusty masses and granules which are found both in the 
cells and lying free, and which become changed in the course of time into 
darker i^igment, are no longer haemoglobin itself, but represent different 
derivatives of haemoglobin. According to their chemical composition 
these derivatives may be divided into two groups, one iron-free, the other 
containing iron. The former is known as lueinaioidin, the latter as hcemo- 
siderin (Xeumann) . 

Hfiematoidin (identical with bilirubin) is a ruby-red (Fig. 104, B) or 
reddish-yellow (Fig. 105, b) pigment occuri ing either in crystalline form, 
or as granules, which may be amorphous, but often show a somewhat 
angular shape (Fig. 105, b), suggesting rudimentary and imperfect crys- 
tals. Haematoidin is soluble in chloroform, carbon disulphide, and 
absolute ether; and insoluble in water and alcohol. It would appear to 
be formed especially when haemoglobin is but slightly exi:)osed to the 
action of living cells, as is especially the case in the centre of large ex- 
travasates and in haemorrhages into the body-cavities, as, for example, 



Fig. 104.—^, Cells containing amorphous blood-pigment : a, 
those with few large fragments of red blood-cells ; /*, c, those 
containing great numbers "of small disintegration-products of red 
blood-cells; J3, rhombic plates and needles of haematoidin. 
X 500. 




tissues, and from it there 
are formed the different 
products which give rise 
to the changes of color in 
the neighborhood of the 
extravasate. A part of 
the absorbed haemoglobin 
may be excreted as urobi- 
lin {urobilinuria) ; another 
part, on the other hand, 
may be precipitated in 
the tissues in the form of 
granules or crystals. The 
latter are yellowish -red or 
ruby-red rhombic plates and 
needles of hcematoidin (Fig. 



THE HEMATOGENOUS PIGMENTS. 237 

into the pelvis of the kidoey or the subdural space. It may be pro- 
duced artificially by the introduction of glass capsules containing blood 
beneath the skin or into the peritoneal cavity in such a way that the 
blood within the capsules may be exposed to the action of the tissue- 
fluids but not of the cells. 

The granules and crystals of hsematoidin are found in the tissues 
either free (Fig. 104, B), or enclosed in cells (Fig. 105, b). In the lat- 
ter case the granules and crystals are usually taken up by phagocytes 
after they have been formed ; though occasionally it may happen that 
the hgematoidin while in solution is taken up by fixed connective- tissue 
cells, for example, cartilage or fat-cells, and then precipitated in solid 
form. 

Haemosiderin, the derivative of the red blood-cells which contains 
iron in demonstrable quantity microscopically, is usually found in the 
tissues as yellow, orange, and brown granules and lumps which become 
darker in the course of time. They are for the greater part contained 
within cells, and in part are formed within the cells. 

When treated with potassium ferrocyanide and dilute hydrochloric 
acid hsemosiderin becomes deep -blue through the formation of Berlin 
blue (ferric oxide salt of hydroferrocyanic acid) (Fig. 105, a). When 
treated with ammonium sulphide there is formed a black sulphide of 
iron. 

Haemosiderin appears to be formed particularly (Neumann) when the 
blood in an extra vasate or in a thrombus is subjected to the action of 
cells ; and it is consequently seen more frequently in small extravasates 
and at the periphery of larger ones. The formation of hsemosiderin maj^ 
take place either within the cells or free in the tissue. The pigment en- 
closed within cells (sideroferous cells) may have been formed from the 




Fig. 105.— Cells containing haemosiderin and hseuiatoidin from an old haemorrhagic focus in the brain. 
(Alcohol, Berlin-blue reaction.) «, Cells containing haeiiwsiderin ; cells containing haeuiatoidin ; c, fat- 
granule cells which have become clear; rt, newly formed connective tissue. X 300. 

remains of disintegrated red blood -eel Is which have been taken up by 
the cells, or from dissolved haemoglobin which has been absorbed by the 
cells. In favor of the latter mode of formation is the diffuse yellow color 
seen in both wandering and fixed cells, which becomes blue when the 
Berlin-blue reaction is applied. Further, when haemoglobin is excreted 
through the kidneys, iron-containing pigment-granules "form in the renal 
epithelium; and moreover fixed cells, as cartilage -cells, for example, 



238 



THE RETROGRADE CHANGES. 



which could hardly be supposed to act as phagocytes and take up frag- 
ments of red cells, often contain granules of hsemosiderin, even when 
lying outside of the immediate neighborhood of the extravasate. 

The free pigment and the pigmented cells cause a distinct pigmenta- 
tion of the extravasate and its immediate neighborhood. The pigmented 
cells soon pass into the lymph-vessels and a metastasis of tJiepig7nent takes 
place, as a result of which the pigment is found in the lymj^h- vessels and 
their neighborhood, and in the lymph-glands where it is found first in the 

free cells of the lymph - 
sinus (Fig. 106). Later 
it may be taken up by 
the fixed tissue -cells. In 
the course of time the 
hseniosiderin is de- 
stroyed and disappears. 
The view which is held 
by many, that hsemosi- 
derin is changed into a 
black melanin, is not 
supported by the actual 
facts. The brownish - 
black granules in the 
lungs, which have been 
explained as due to such 
a change, are found 
through high magnifica- 
tion (Neumann) to consist of one or several minute particles of carbon 
surrounded by a coating of haemosiderin. 

If hsemosiderin is brought into contact with hydrogen sulphide it be- 
comes black ; and as the result of such reaction there may be produced 
in the cadaver black and green spots or a more diffuse discoloration, 
which are known as pseudomelanosis. It is observed most often in the 
intestine, peritoneum, and in suppurating wounds, since in these regions 
hydrogen sulphide is more likely to be formed in the course of putrefac- 
tion. 

Arnold has recently declared that, both in lijBmatogenous and exogenous siderosis 
(see § 72), the ii'on-granules of the sideroferous cells (leucocytes, connective-tissue cells, 
liver-cells, etc.) are not iron-granules which have been taken up from without through 
phagocytosis, or which have been precipitated within the cells, but are changed cell- 
plasmosomes which have taken up the iron, converted it, and combined it with them- 
selves. The statements made in the main text (§§ 71 and 72) as to the genesis of a por- 
tion of the sideroferous cells harmonize with Arnold's view, but it must be affirmed 
that a formation of sideroferous cells through phagocytosis also occurs, both in case of 
extravasates and iigemachromatoses due to intravascular destruction of the red blood- 
cells. 

The black pigment of pseudomelanosis is regarded by many authors as a sulphur 
compound of iron which is formed through the action of hydrogen sulphide upon the 
blood. According to investigations by E. Neumann, pseudomelanin is not caused by a 
cadaveric decomposition; but its formation is dependent upon local conditions, the 
chief of which is that the iron-containing products of the destruction of haemoglobin 
must be formed during life, whereby the haemosiderin when exposed after death to the 
action of hydrogen sulphide assumes a black color. According to investigations by 
Zeller, Arnold, and Ernst, black pigment maj^ also be formed during life, through the 
action of bacteria which produce hydrogen sulphide. 




Fig. 106.— Accumulation of pigment-containing cells in the 
lymph-glands after resorption of an extravasate of blood. (Miiller's 
riuid, carmine.) a, Cortical node; Z), lymph-sinus; c, cells con- 
taining pigment-granules. X 100. 



THE HEMATOGENOUS PIGMENTS. 



239 



Literature. 

{Hcematogenous Figments. ) 

Arnold: Siderofere Zellen. Anat. Anz., xvii. ; Yirch. Arch., 161 Bd., 1900. 
Borst: Melanose des Pericardiums (Epithelpigmentirung). Virch. Arcli., 147 Bd., 
1897. 

Cordua: Ueber den Resorptionsmechanismus von Blutergiissen, Berlin, 1877. 
Diirck: Veritnderungen d. Blutungeu im Ceutralnervensystem. Vircli. Arcli., 130 
Bd., 1892. 

Ernst: Pseudomelanose. Virch. Arch., 152 Bd., 1898 (Lit.). 

Gabbi: Le cellule giobulifere nel loro rapporti alia fisiologia del sangue, Firenze, 1891. 
Langhans: Resorption der Extra vasate u. Pigmentbildung. Virch. Arch., 49 Bd. 
1870. 

Miihlmann: Pigmentmetamorphose der rothen Blutkorperchen. Virch. Arch., 126 
Bd., 1891. 

Neumann, E. : Beitrage zur Kenntniss der pathologischen Pigmente, ib., Ill Bd., 

1888; Das Pigment der braunen Limgeninduration, ib., 161 Bd., 1900. 
Perls: Nacliweis von Eisenoxyd in gewissen Pigmenten, ib., 39 Bd., 1867. 
duincke: Deut. Arch. f. klin. Med., 25, 27, and 33 Bd. 

Schmidt: Verwandtschaft d. haraatogenen u. autochthonen Pigmente. Virch. Arch., 
115 Bd., 1889; Hamorrhagie u. Pigmentbildung. Ergebn. d. allg. Path., iii., 1897. 
Skrzeczka: Ueber Pigmentbildung in Extra vasaten. Beitr. v. Ziegler, ii., 1888. 
Vircliow: Die pathologischen Pigmente. Virch. Arch., 1 Bd., 1847. 
Vossius . Grirnliche Farbung der Cornea nach Traumen. Oracle's Arch., 35 Bd., 1889. 
Zeller u. Arnold: Pseudomelanotische Abscesse. Virch. Arch., 139 Bd., 1895. 
Ziegler: Untersuchungen liber die Herkunft der Tuberkelelemente, Wiirzburg, 1875. 



§ 72. When large numbers of red blood=celIs break down in the 
circulating blood, a portion of the dissolved hfeinoglobiii or methsemo- 
globin may pass into the plasma, or, on the other hand, fragments of red 
cells may be carried about in the circulation. Such a destruction of red 
cells occurs to a marked degree in poisoning with arsenic, toluylendia- 
min, potassium chlorate, and morels ; to a lesser degree in other diseases, 
such as many infections, malaria, pernicious anaemia, and in overheating 
of the body. The passage of 
haemoglobin or methaemoglobin 
into the blood-plasma leads to 
the condition of hcemogloMn- 
cemia, in which the blood- 
plasma is colored red. When 
the amount of dissolved hae- 
moglobin in the blood is large, 
a portion may be excreted 
through the kidneys, giving 
rise to hcemoglobimcria or meth- 
cemoglohinuria, in which con- 
ditions the urine may present 
a bloody ap]3earance, or a color 
varying from a clear brownish - 
red to a dark reddish-black. 
This occurs particularly in the 
case of the first-named poisons, 

but also occasionally after the action of other injurious influences, as, for 
example, after exposure to cold (periodical haenioglobinuria). 

V^^hen formed produets arise from the disintegration of the red cells, 
as, for example, after extensive burns, such fragments collect in the 




Fig. 107.— Infiltration of the cells of the liver-rods with 
yellow haemosiderin granules, from a case of pernicious 
ansemia. (Osmic acid.) a, Heemosiderin ; 7), cells in a 
state of fatty degeneration. X 2-50. 



240 



THE RETROGRADE CHANGES. 



capillaries of the liver, spleen, lymph-glauds, and bone-marrow, and to 
a less extent in other organs ; and are sooner or later taken up by cells. 

As the result of an increased supply of hsemoglobin to the liver the 
functional activity of this organ is increased, so that the amount of biJe- 
pigment in the bile may be much greater than normal; and under certain 
conditions oxyhaemoglobin may appear in the bile (Stern). When the 
blood-destruction is very great, the liver may not be able to dispose of 




Fig. 108.^H£emoehromatosis of the liver. (Alcohol, carmine.) a, Acini; h, peritoneum ; c, branches 
of the portal vein ; (/jutiltrated periportal connective tissue ; e, pigment lying within the liver-acini ; /, 
central veins, x 20. 

all the blood-pigment brought to it; and in consequence derivatives of 
haemoglobin are deposited, partly in the liver and partly in other organs, 
or may be in part excreted by the kidneys. In this way there may arise 
a more or less extensive hasmochromatosis of different organs, the cells 
of which show an ochre-yellow or brown color. 

The derivatives of hgemogiobin deposited in this way are partly iron- 
free 2y'i'gmeiits and partly hcemosiderin ; but the latter is particularly a 
frequent cause of pigmentation of tissues, and it is, therefore, proper to 
speak of a pigmentation by hsematogenous siderosis. 

These deposits of iron=containing pigment are chiefly in the liver, 
where they appear partly in the form of yellow granules and lumps, 
which are for the greater part enclosed in leucocytes lying within the 
liver -capillaries. Further, they are found also in the form of fine yellow 
granules, which give the iron-reaction, in the endothelial cells of the 
capillaries (to which the stellate cells of Kupffer belong), and in the 
liver-cells (Fig. 107, a). In many diseases, as, for example, pernicious 
malaria or pernicious ansemia, the majority of the liver-cells contain 
such j)igment, so that the liver through the j)resence of so much iron 
takes on a characteristic yellowish-brown color. 

When large quantities of the i^roducts of the disintegration of red 



HEMOSIDERIN. 241 

blood -eel Is are brought to the liver, they accumulate particularly in the 
periportal connective tissue and in the periphery of the acini (Fig. 108, 
d, e). The lumps or granules of iron-containing pigment lie either free 
in the capillaries, or in the tissue ; or are enclosed within leucocytes, 
liver-cells, connective-tissue cells, or the capillary endothelial cells. 
The infiltrated area presents to the naked eye a reddish-brown, rusty 
color. 

The iron-pigment which is carried to the spleen is deposited chiefly 
in the pulp within free cells ; but granules are also found in the fixed 
cells. In the lymph-glands the iron granules are found chiefly in the free 
cells of the lymph -channels. In the hone-marrow retained hsemosiderin 
(Fig. 109) is found partly in free cells lying within the capillaries, and 
partly in the endothelium, also partly in the marrow-cells ; the number 
of iron- containing cells may be very marked. 

In the kidneys the hsemosiderin granules are most abundant in the 
epithelium of the convoluted tubules (Fig. 110, a), but they are also 
found in the lumina of the urinary tubules (&), in the epithelium of 
Bowman's capsule (e), and in the endothelium of the capillaries. If 
small particles of hsemosiderin are present in the circulating blood, they 
will usually be found in the kidney- vessels. When haemoglobin is ex- 
creted by the kidney, drops of this substance will be seen lying in the 
tubules. In cases of marked deposit of pigment the kidney may show a 
distinct pigmentation even to the naked eye. 

The haemosideriu, which is found in the different tissues, has been 
brought to them in the form of small lumps or granules, and is contained 
chiefly in leucocytes. On the other hand, another part of the iron-gran- 




FiG. 109.— Hifiinosiderin deposit in the bone-marrow (mixed fatty and lymphoid marrow), in icterus. 
(Alcohol, carmine, Berlin-blue reaction.) X 300. 

ules is precipitated in solid form within the cells from substances brought 
to them in solution. Since the cells (liver-cells, kidney epithelium, en- 
dothelium of the blood-vessels, and the cells of the lymph-glands, bone- 
marrow, and spleen) not infrequently show a diffuse iblue color after the 
iron- test has been applied, the iron must be diffused throughout the cell- 
protoplasm, and is probably converted later into the granular form. It 
is also possible that the diffuse coloration may arise in part from a solu 



242 THE RETROGRADE CHANGES. 

tion of iron within the cells. According to the observations of different 
anthors it is assumed that besides the colored deposits of pigment, color- 
less granules of an iron-albuminate may be present in the cells. This 
theory is supported by the observation that more pigment granules are 
visible after the iron reaction has been applied, than could be seen 
before. 

The deposit of iron=free pigments, hcematoidin or hUinibin is not of 
frequent occurrence in hiemochromatosis, but occasionally j^ellow gran- 
ules which do not give the iron reaction are found in the organs named 
above ; and it may, therefore, be assumed that the pigment in part may 
be constantly free from iron. 

By the majority of authors (see Geyer, loc. cit.), the mottled 'pigmentation of the skin 
which develops in chronic arsenic poiso//in(j, and which is due to the deposit of small 
yellowish-brown pigment granules in the corium and epidermis (similar to the pig- 
mentation of Addison's disease), is to be classed with the ha'mochromatoses. It is to 
be referred to the degenerative intluence of arsenic upon the bone-niarrow and the 




Fig. 1 U).— HaMnatogenous deposits of iron in the kidney in pernicious malaria (contracted in Basra- 
mayo). (Alcohol, carmine, Berlin-blue reaction.) a. Convoluted tubules, whose epithelial cells contain 
iron granules and are stained dilTusely blue; h, iron-g-ranules in the lumen of the tubules ; c, straight tub- 
ules; d, glomerulus ; e, epithelium of the capsule, containing iron-granules. X 150. 

blood. It should be noted, however, that the pigment does not give the iron reaction, 
and that, according to other observations, pigment in epithelium which is derived from 
haemoglobin is not permanent. 

The organism supplies its need for iron through the assimilation of the iron 
compounds found in the iron -containing articles of food. The iron contained in the 
iron preparations used for medicinal purposes is absorbed from the small intestine, in 
particular from the duodenum. Iron absorbed in excess is in part stored up as ha-mo- 
siderin in the spleen, bone-marrow, and lymph-glands, or temporarily in the liver; and 
in part excreted through the kidneys, liver, and large intestine. 

In malaria tn'o pigments are formed as a result of the destruction of the red cells by 
the malarial parasite. One of these is formed by the malarial Plasmodium itself, is 
contained within the parasite, is black, and gives no iron reaction. Its nature is not 
known. 

The second pigment is h^emosiderin, which passes into the blood-plasma as the re- 
sult of the destruction of the red blood-cells, and is deposited in the liver, spleen, and 
bone-marrow. In cases of marked destruction of the blood there may occur also a side- 
rosis of the kidneys (Fig. 110), and an excretion of iron in the urine. 

The ///■( ( // riflar irltich is observed ill the neighborhood of llood-c<nit(ii ni ng rcsseh in de- 
composing cadavers is to be referred to a formation of sulphur-metluemoglobiu through 



HJEMOSIDERIN. 



243 



the action of H2S on oxyhsemoglobin {Hoppe-Seyler, Harnack). In the absence of oxy- 
gen, sulphur-h£Bmoglobiu is formed, wliich possesses a dark-red color {Harnack). 



Literature. 

(Kwmochromatosis ; Iron Absorption ; Deposit and Excretion. ) 

Afanassiew : Toluylendiaminvergiftung. Zeitschr. f. klin. Med., vi. ; Mit Hamoglo- 
binurie iind Ikterus verbimd. Vergiftungen. Virch. Arch., 98 Bd., 1884. 

Alexander: Eisengehalt d. Milz- u. Lymphdriissen. Inaug.-Diss., Freiburg, 1895. 

Auscher et Lapicque: Accumul. d'hydrate ferrique dans I'organisme. Arch, de 
phys., viii., 1896. 

Arnstein: Ueber Melanamie und Melanose. Yirch. Arch., 61 Bd., 1874. 
Baserin: Eisengehalt der Galle bei Polycholie. Arch. f. exp. Path., xxiii., 1887, 
Biondi: Ablagerung von Hamosiderin bei Hamatolyse. Beitr. v. Ziegler, xviii., 1893 
(Lit.). 

Bostrom: Intoxication durch die essbare Morchel, Leipzig, 1882. 
Cloetta: Eisenresorption im Darm. Aich. f. exp. Path., 38 Bd., 1897. 
Dutton: Iron in the Liver and Spleen in Malaria. Journ. of Path., v., 1898. 
de Filippi: Unters. uber das Ferratin. Beitr. v. Ziegler, xvi., 1894. 
Gaule: Resorption des Eisens. Deutsch. med. Woch., 1896. 

Geyer: Die chron. Hautveranderungen bei Arsenicismus. Arch. f. Derm., 43 Bd., 
1898 (Lit.). 

Grimm: Urobilin \m Harn. Virch. .Arch., 132 Bd., 1893. 

Harnack: Einflussd. Schwefelwasserstoffs auf d. Blutfarbstoff. Zeit. f. phys. Chem., 
26 Bd., 1898. 

Heuss: Keratosis u. Melanosis nach Arsengebrauch. Correspbl. f. Schweizer Aerzte, 
1894. 

Hindenlang: Pigmentinfiltration bei Morb. macul. Werlhofii. Virch. Arch., 79 Bd., 
1880. 

Hintze: Hamochromatose. Virch. Arch., 139 Bd., 1895. 

Hochliaus u. Q,uincke : Eisenresorption u. Ausscheidung im Darm. Arch. f. exp. 

Path., 37 Bd., 1896. 
Hofmann: Eisenresorption u. Ausscheidung. Virch. Arch., 151 Bd., 1898. 
Hoppe-Seyler: Abscheidung des Urobilins in Krankheiten. Virch. Arch., 114 Bd., 

1891. 

Hunter: Action of Toluylendiamin. Journ. of Path,, iii., 1895. 

Ja,cob: Ueber Siderosis. Inaug.-Diss., Freiburg, 1895. 

Kober: Ueber das Eisen in diatetischer Hinsicht. Deut. med. Woch., 1894. 

Kobert: Argja-ie u, Siderosis. Arch. f. Derm., 1893. 

Kunkel: Farbstoff im Harn. Virch. Arch., 79 Bd. ; Pigmentinfiltration, ib., 81 Bd., 
1880. 

Marchand: Giftige Wirkung d. chlors. Salze. Arch. f. exp. Path., 22 and 23 Bd., 
1886, 1887. 

V. Mering: Das chlorsaure Kali, Berlin, 1885, 

Minkowski u. Naunyn: Ikterus durch Polycholie. Arch. f. exp. Path,, 21 Bd,, 

1886. 

Moroni: Siderosi epatica. Arch, per le Sc. Med,, xvii., 1893, 
Mliller: Arsenmelanose. Arch, f. Derm., 25 Bd., 1893. 

Nasse : Die eisenreichen Ablagerungen im thierischen Korper, Marburg, 1889. 
Nathan: Aufnahme u, Ausscheidung d. Eisens d, Eisensomatose. Deut. med. Woch,, 
1900. 

Neumann: Bilirubinkrystalle im Blute neugeborener und todtfauler Friichte. Arch. 

d. Heilk., x., 1869; Das melanamische Pigment. Virch. Arch., 116 Bd., 1889. 
Nielsen: Melanosis arsenicalis. Monatsh. f. prakt. Derm., xxiv., 1897. 
Opie: Hamochromatosis. Journ. of Exp, Med., iv., 1899. 

Peters: Elsenablagerungen bei versch. Krankheiten. Deut. Arch. f. klin. Med., 32 Bd., 
1882. 

Ponfick: Hamoglobinamie. Berl. klin. Woch., 1877, 1883. 

auincke: Zur Pathologic des Blutes. Deut. Arch. f. klin. Med., 25, 27 and 33 Bd. ; 
Perniciose Anamie. Klin. Vortr., No. 100, 1876; Eisen therapie. Klin. Vortr., No. 
129, Leipzig, 1895. 

Scheimpflug: Beitr. z. pathol. Histologic des Darms, Zeitschr. f. klin. Med., ix., 
1885. 

Schurig: Schicksale des HSmoglobins im Organismus. Arch. f. exp. Path., 41 Bd., 

1898. 



244 THE RETROGRADE CHANGES. 

Stadelmann : Der Ikterus, St'ifctgart, 1891. 

Stern: Ueber das Auftreten von Oxyhamoglobin in der Galle. Virch. Arch., 123 Bd., 
1891. 

Stiihlen: Eisengehalt versch. Organe bei Anamie. Deut. Arch. f. klin. Med., 54 Bd., 
1895. 

Tedeschi: Das Eisen in d. Organen normaler u. entmilzter Thiere. Beitr. v. Ziegler, 
xxiv., 1898. 

Wyss: Ueber Arsenraelanose. Correspbl. f. Schweizer Aerzte, xx., 1890. 
Zahn: Ueber Pigmentintiltration der Knorpel. Virch. Arch., 72 Bd., 1878. 
Zaleski: Eisengehalt der Leber. Zeitr. f. phys. Chem., x., 1886; Zur Eisenfrage. 

Virch. Arch., 104 Bd,, 1886; Ausscheidung des Eisens. Arch. f. exp. Path., xxiii., 

1887. 

§ 73. Icterus or jaundice is a pathological pigmentation of the tissues 
due to the presence of bile -pigment. Icterus is a symptom which occurs 
in the course of numerous diseases of the liver, and is of frequent occur- 
rence even in the first days of life {icterus neonatorum). 

The pathological pigmentation which characterizes icterus is apparent 
during life, particularly in the skin, conjunctiva, and in the urine; in 
the cadaver the internal organs — the serous membranes, lungs, kidneys, 
liver, the subcutaneous and intermuscular tissues, the blood plasma, 
clots lying in the vessels, etc. — may show an icteric coloration. In 
recent cases the icteric color is yellow; in long-standing cases the skin 
takes on an olive-green or dirty grayish-green color, while similar color- 




FiG. 111.— Obstructive icterus of the liver, due to compression of the ductus choledochus by a cancer 
of the gall-bladder. (Sublimate, alum-carmine.) n, Intra-acinous bile-capillaries, moderately dilated and 
filled with bile ; ft, widely dilated intra-acinous bile-capillary, containing large mass of pigment ; c, bile- 
pigment in the liver-cells cl, dj, endothelium stained with bile-pigment; e, desquamated endothelium 
stained with bile-pigment ; /, pigment mass surrounded by cells ; g, rupture of the pigment contained in a 
bile-capillary into a blood-capillary. X 365. 

ations occur in the internal organs, particularly in the liver, and occa- 
sionally in the kidneys. 

Icterus results f rom the entrance of bile — that is, of bile-pigment (bilirubin) 
— into the blood and fluids of the body. During such a condition the urine 
excreted contains elements of the bile, particularly the bile- pigments. 



HEPATOGENOUS PIGMENT: ICTERUS. 



245 



Icterus is a hepatogenous disease, inasmuch as the bile -pigments have their 
source in the liver. As the result of disease processes in the biliary 
passages or in the liver itself the normal outflow of the bile is hindered, 
and the bile is then taken up into the lymphatics and blood-vessels of 
the liver. Such a damming back of the bile may be caused, for exam- 
ple, by a narrowing or closure of the large bile -ducts through the forma- 
tion of scar-tissue, through gall-stones wedged in the lumen, or through 
tumors developing in the bile -ducts themselves, or arising outside of the 
ducts and compressing them; or through inflammatory processes, ab- 
scesses, connective-tissue growths, or tumors of the liver which compress 
or pull upon, or completely obliterate the smaller bile-ducts, and in this 
way hinder the outflow of blood from the smaller bile-ducts and capil- 
laries. 

When through obstruction of any kind the bile is dammed back into 
the intrahepatic bile-passages, namely, into the bile- capillaries, there 
may occur in the flrst place a resorption of bile through the lymphatics 
of the liver. As the condition progresses the bile accumulates more and 
more in the intra-acinous bile-capillaries (Fig. Ill, a, b) and in the liver- 
cells themselves (c), so that finally the masses of bile-pigment (g) may 
breakthrough into the blood-capillaries, the point of rupture often being 
demonstrable microscopically. Following this the endotheliam of the 
blood-capillaries may also become jDigmented (d, dj. 

According to recent investigations regarding the structure of the 
liver, the intracellular bile -capillaries extend into intracellular seeretion- 
vacuoles (von Kupffer, Pfeiffer) from which are given off extremely fine 
intracellular secretion- canaliculi (iiTauwerck, Stroebe, Browicz) surround- 
ing the nucleus as with a meshwork. On the other side the liver-cells 
stand in the closest relationship to the blood-capillaries. Normally, a 
double secretion takes place in the liver, an external one of bile-acids 
and pigment into the bile -passages, and an internal one of sugar and 
urea (Minkowski) into the blood-vessels. IS'auwerck is of the opinion 
that this latter secretion is also carried through a network of extremely 
delicate intracellular canaliculi. It is, therefore, easy to understand that 
disturbances of secretion are of not infrequent occurrence, and that a pas- 
sage of bile into the blood maybe caused, not only through a stasis of the 
bile, but also through diseased conditions of the liver- cells due to infec- 
tions or intoxications. Besides the icterus due to stasis of the bile, or stasis- 
^ parapedesis (Minkowski), there may, therefore, be distinguished an icterus 
due to a toxic or infectious parapedesis of the bile (paracholia, Pick). It is 
probable that many forms of icterus, which were formerly believed to be 
caused by a catarrhal condition of the bile-passages, are to be interpreted 
as belonging to the second class. 

It is also possible that disturbances of innervation and of the circula- 
tion of the liver may be sufficient to bring about an escape of bile into 
the intra-acinous lymph -channels or into the blood, so that a nervous 
paracholia may also be distinguished. 

In paracholia of long standing and of a marked severity, as occurs 
particularly in cases of permanent closure of the bile-passages, not only 
do the liver-cells become pigmented, but also the endothelium of the 
blood-vessels (Fig. Ill, d, dj. As the result of such pigmentation the 
cells not infrequently become desquamated (e), and lie free in the ves- 
sels. 'Not rarely degenerative changes, cell-necroses, inflammation, and 
proliferation of the connective tissue are also associated with the biliary 
stasis. 



246 



THE RETROGRADE CHANGES. 



When bile-pigment, either in solution or in the form of granules and 
lumps, obtains entrance to the blood, the tissues of the body become grad- 
ually permeated with bile-stained lymph, and thereby acquire an icteric 
color. If phagocytes containing granules or lumps of bilirubin are 
present in the circulating blood, they may accumulate here and there, 
* particularly in the spleen and the bone -marrow. After a time the 
bile-pigment held in solution within the tissue-lymph may become pre- 
cipitated as solid particles of bile-pigment, chiefly in a granular form, but 
rarely in a crystalline (the latter form occurs almost entirely in the 
new-born, in which the crystals are found in the fixed and wandering 
cells of the connective tissue, in the liver-cells, and in the renal epithe- 
lium). The crystals are in the form of rhombic plates and needles, 
similar to those of haematoidin (Fig. 104). In severe cases of icterus 
very many of the tissue-cells contain pigment, and, as a result of the 




Fig. 113.— Icterus of the kidney in obstructive jaundice. (Sublimate, carmine.) a. Tubular epi- 
thelium containing yellowlsh-brown granules ; b, large casts stained yellowish-green ; c, cast containing 
pigmented cells ; d, desquamated epithelium containing bile-pigment granules. X 200, 

metastasis of cells containing pigment, accumulations of the latter in the 
lymph-glands may occur. 

In the kidneys in which bile -pigment is being excreted there likewise 
occurs an excretory pigmentation, particularly of the epithelium of the 
urinary tubules (Fig. 112, a, d), which in consequence may become 
desquamated. If, as the result of the damage done to the secreting cells 
through the excretion of the bile-pigment, there are formed, as is usually 
the case, hyaline casts — ^that is, hyaline coagula in the albumin -contain- 
ing urine in the tubules — these likewise become colored by the bile-pig- 
ment (Fig. 112, b, c). 

Associated with the deposits of bilirubin in icterus there is always a 
deposit of hemosiderin which may become so abundant, particularly in the 
bone-marrow (Fig. 109), spleen, and lymph-glands, and occasionally also 
in the liver, that the pigmentation of the organs named is dependent in 
part upon iron-pigment. 



HEPATOGENOUS PIGMENT: ICTERUS. 



247 



When au increased destruction of red blood- cells takes place within the 
blood-vessels, hiematoidin or bilirubin, in addition to hsemosiderin, is 
formed in different parts of the body (see § 72) ; but the formation of 
bilirubin outside of the liver is very slight and is not sufficient to cause 
any extensive icteric coloration of the tissue, so that a purely hwmatoge- 
nous jaundice does not occur. The liver is the great elaborator of bilirubin, 
and in cases of increased destruction of the blood -cells the liver-function 
is increased and there is an increased production and excretion of bile- 
pigment. An icterus due to increased destruction of blood-cells can occur 
only when at the same time there are present in the liver such changes 
as cause a imssage of the bile into the blood. 

The question as to whether there is a hgematogenous as well as a hepatogenous 
jaundice has long been an object of discussion, and remains unsettled at the present 
time, in spite of numerous experimental investigations directed toward its solution. 
Since, as a matter of fact, bilirubin may be formed in the most different kinds of tissue 
from extra vasated blood, the occurrence of a haematogenous icterus would a priori ap- 
pear very probable. Experimental investigations as to the results of the destruction of 
red cells in the circulating blood, particularly through the action of arsenic, toluylen- 
diamin, and potassium clilorate, have shown that the derivatives of blood-pigment 
which are formed in the tissues and there retained for a long time are essentially iron- 
containing pigments (hsemosiderin), while the production of bilirubin is practically con- 
fined to the liver, which for the time being secretes an increased amount of richly pig- 
mented bile. 

According to the investigations of Minkoicski and JS'aunyn, the urine of geese and 
ducks after removal of the liver contains no bile-pigment — a fact which would indicate 
that the transformation of blood-pigment into bile-pigment is ordinarily confined to the 
liver. The inhalation of arseniureted hydrogen for a few minutes is sufficient to produce 
in geese in a very short time an intense polycholia and hgematuria, the urine containing 
haemoglobin in solution, disintegrating red cells and biliverdin. If the liver from such 
a goose be removed, the biliverdin quickly disappears from the urine, and no trace of 
bile- pigment can be demonstrated in the blood. It is therefore evident that in arsenic 
poisoning the formation of the bile-pigment is confined to the liver, in which organ 
leucocytes enclosing iron-containing fragments of broken-down red cells are found to 
be present. 

In so far as it is possible to judge from the experimental investigations which have 
been made up to the present time, a pure haematogenous jaundice does not appear to 
occur. The mere fact of the occurrence of jaundice after intoxications, inhalation of 
ether and chloroform, transfusion of blood, snake-bite, septicaemia, typhoid fever, yel- 
low fever, paroxysmal haemoglobinuria, etc., cannot be taken as proof of the existence 
of a haematogenous jaundice. There is, indeed, in these conditions an increased destruc- 
tion of red blood-cells; but bilirubin is essentially a product of the liver, and if jaundice 
occurs it can be due only to the fact that a portion of the bile-pigment, which is pro- 
duced in excess, has found its way into the blood. It appears that a change in the con- 
sistency of the bile is sufficient {Stadelmann) to cause an absorption of bile-pigment into 
the blood. 

Literature. 

{Icterus.) 

Auld: Hag matogenous Jaundice. Brit. Med. Journ., i., 1896. 

Birch-Hirsclifeld: Die Entstehung der Gelbsucht neugebor. Kinder. Virch. Arch., 
87 Bd., 1882. 

Browicz: Intracellulare Gallengange, etc. Deut. med. Woch., 1897: Cbl. f. allg. 

Path., 1898; Lebercapillaren. Bull, de I'Ac. des sc. de Cracovie, 1900. 
Dastre et Floreseu: Pigments biliaires. Arch, de phys., ix.. 1897. 
Halter u. Lauterbacher : Resorptionsikterus beimFrosch. Beitr. v, Ziegler, x., 1891. 
Harley: Pathology of Obstructive Jaandice. Brit. Med. Journ., 1892; Leber u, Galle 

wahrend dauernden Verschlusses von Gallen- und Brustgang. Du Bois-Reymond's 

Arch., 1893. 

Hofmeier: Die Gelbsucht der Neugeborenen. Zeitschr. f. Gebh. u. Gyn., viii., 1882. 
Kiener et Engel: Pathogeuie de I'ictere et ses rapports avec I'urobilinurie. Arch, de 
phys., X., 1887. 



248 



THE RETROGRADE CHANGES. 



Kiihne: Beitrage zur Lelire vom Ikterus. Vircli. Arch., 14 Bd., 1858. 
Kunkel: Ueber das Auftreten verscliiedener Farbstolfe im Haru. lb., 79 Bd., 1880. 
Lesage et Demelin: L'ictere da nouveau-ne. Rev. de med., 1898. 
Lowit: Bildimg- des Gallenfarbstoffs in d. Frosclileber. Beitr. v. Ziegler, iv., 1889. 
Minkowski: Die Storungen der Leberf unction. Ergebn. d. allg. Path., Jahrg. ii., 
1897. 

Minkowski u. Naunyn: Pathologie d. Leber u. d. Il^terus. Arch. f. exp. Path., 

xxi., 1886. 

Nauwerck: Leberzellcn u. Gelbsucht. Miinch. med. Woch., 1897. 

Neumann: Abscheidung von Bilirubinkr3^stallen aus dem Blute in den Geweben. 
Arcli. d. Heillv., viii., 1867; Bilirubinkrj^stalle im Blute der Neugeborenen u. todt- 
fauler Frlichte. lb., ix., 1868; ib., xvii., 1876; Ikterus neonatorum. Virch. Arch., 
114 Bd., 1888. 

Neumeister; Physiologische Chemie, Jena, 1897. 

Orth: Ueb. d. Vorkommen v. Bilirubinlaystallen bei neugeb. Kindern. Virch. Arch., 
63 Bd., 1875. 

Pick: Entstelmng d. Ikterus. Wien. klin. Woch., 1894; Wesen d. Ikt. Prag. med. 
Woch., 1895. 

duincke: Beitrage zur Lehre vom Ikterus. Virch. Arch., 95 Bd., 1884; Ueber die 

Entstehung der Gelbsucht Neugeborener. Arch. f. exp. Path., xix., 1885. 
Roger: Physiol, norm, et pathol. du foie, Paris, 1893. 
Runge: Die Krankheiten der ersten Lebenstage, Stuttgart. 1893. 
Silbermann: Die Gelbsucht der Neugeborenen. Acrh. f. Kinderheilk. , viii., 1887. 
Stadelmann: Der Ikterus, Stuttgart, 1891. 

Stern: Ueber die norm. Bildungsstatte des Gallenfarbstoffs. Arch. f. exp. Path., xix., 
1885. 

Szubinski: Structur der Leberzellen. Beitr. v. Ziegler, xxvi., 1899. 
Wertheimer et Lepage: Absorption des pigmentes dans le foie. Arch, de phys., 
1897. 

§ 74. Pigmentation of the tissues through substances introduced 
into the body from without occurs \yhen substances possessing a color 
of their own gain entrance in some manner to the tissues, where they are 
able to remain for some time without suffering changes. The number of 
such substances is large, and the manner of entrance varied. The most 
common avenues of entrance are the lungs, ivounds, and intestinal tract. The 




Fig. 113.— Deposit of cinnabar in tattooed skin. (Alcohol, alum carmine.) a. Epithelium; i», corium; 

c, cinnabar. X 80. 

most familiar pigmentation through wounds is tattooing of the sMn, which 
is frequently practised by individuals of civilized as well as of uncivil- 
ized nations. 

The method of tattooing colored figures, etc., consists in the intro- 
duction of insoluble granular pigments, such as carbon, cinnabar, etc., 
into slight wounds of the skin. The pigments are rubbed into the 



EXTRINSIC PIGMENTS. 



249 



'9 B . 



- @ 



wounds, whence they penetrate and infiltrate the tissue in their imme- 
diate neighborhood. A portion of the pigment remains in the corium 
(Fig. 113, c) ; another portion is carried to the lymph-glands, which 
thereby become pigmented. 

The lungs and their lymph-glands may become intensely pigmented 
through the inhalation of colored dust, such as coal-dust, soot, iron-dust, 
etc. Through the inhalation of coal-dust the lungs may become wholly 
black. 

When coal-dust is taken into the lungs in the respired air a portion 
of the pigment is carried to the peribronchial lymph-glands, which in 
consequence may become black. When the deposit is very abundant the 
lymph-glands may undergo softening. 

If the glands are situated in the ^* ^ a 

neighborhood of a vein, the pigment- ^ ® % % ^ ^ 

deposit and the softening may in- | % ^ I 

A^olve the vein-wall, so that finally g % § ' f' %. 

particles of coal-dust may pass into ^ |f © 

the blood-stream, and be carried to J % @ @ 

other organs, the spleen, liver, and 
bone-marrow (see § 21). 

From the intestine only soluble sub- 
stances are absorbed, and a perma- 
nent pigmentation can therefore oc- 
cur, only when these are precipitated 
in the tissue in a solid form, which 
is at the same time either black or 
possessing some color. The most fre- 
quent of such pigmentations is that 
known as argyria, which is due to the 
long -continued use of silver-prepara- 
tions. In this condition the skin may 
show an intense grayish-brown discol- 
oration, and the internal organs may 
also present more or less pigmenta- 
tion. The silver is deposited in the 
ground-substance of the tissues in the 
form of fine granules, more especially 
in the glomeruli, and the connective 
tissue of the medullary pyramids (Fig. 
114, b), the intima of the great ves- 
sels, adventitia of the smaller ones, in 

the neighborhood of the mucous glands, the papillae of the skin, con- 
nective tissue of the intestinal villi, and in the choroid plexus of the 
lateral ventricles. Deposits may occur also in the serous membranes, but 
the epithelial tissues, the brain, and the cerebral vessels escape. Exten- 
sive deposits of silver pigment in the medullary portion of the kidneys 
may lead to the formation of hyaline connective tissue, which may 
undergo calcification. 

Under especial conditions iron, when taken into the body in excessive 
amounts, may be deposited in the bone-marrow, spleen, and lymph - 
glands ; but the pigmentation thus produced is only rarely visible to the 
naked eye. In lead-poisonhig there may be seen a grayish- black discolor- 
ation of the gums, which is due to the deposit of granules of sulphide of 
lead in the connective tissue of the mucous membrane. They are pro- 



Fig. 114.— Deposits of silver In the pyramidal 
portion of a rabbit's kidney, after seven months' 
administration of silver salts (experiment by von 
Kahlden.) (Alcohol. hEematoxylin.) a. Epithe- 
lium of the collectinor tubes ; b, connective tissue 
with brown silver granules. X 500. 



250 



THE RETROGRADE CHANGES. 



duced through the action of hydrogen sulphide upon the lead, which is 
present in solution in the mucous membrane. 

Literature. 

(Argyria.) 

Behrend: Argyrie. Eiilenburg's Realencyklopiidie, 1894. 
Frommann: Eiu Fall von xligyiia. Vircli. Arcli.. 17 Bd., 1859. 

Jacobi: Aut'nahnie der SilberDraparate in dea OrgaDismus. Arch. f. exp. Path., viii., 
1878. 

Jahn: Argyrie. Beitr. v. Ziegler, xvi., 1894. 

V. Kahlden: Ablagerung des 8ilbers in den Nieren. Beitr. v. Ziegler, xv., 1894. 
Kobert: Ueber Argyrie ii. Siderosis. Arch. f. Derm., 25 Bd., 1898. 
Levin: Ueber locale Gewebe-Argvrie. Berlin, klin. Woch., 1886. 
Riemer: Ein Fall von Argyrie. Arch. d. Heilk., 16 Bd., 1875. 
Huge: Ueber den Bleisaum. Deut. Arch. f. klin. Med., 58 Bd., 1898. 
Warthin: Argyria. Kef. Handb. of Med. Sc., 1901. 

XV. The Pathological Absence of Pigment. 

§ 75. The absence of pigment occurs, in the first place, as a congeni- 
tal condition, and is then termed albinism or leucopathia congenita. 

In a part of such cases the absence of 
pigment extends over the entire body 
(alhinismus universalis, Kakerlaken, albi- 
nos) ; in other cases it is restricted to cer- 
tain portions of the skin (albinismtis par- 
tialis). In those parts of the skin which 
are destitute of pigment the hairs likewise 
may contain no pigment, and appear 
white or yellowish-white {2)oJiosis or leu- 
cotrichia congenita universaJts, or circum- 
scripta). In universal albinism the pig- 
ment of the retina, choroid, and iris may 
also be wanting, so that consequently the 
choroid, from the amount of blood which 
it contains, appears red, and the iris, ac- 
cording to the angle of observation and 
the degree of illumination, will appear 
either bluish-white or red. On micro- 
scopical examination no pigmented cells 
can be found. 

A second form of absence of pigment 
is that condition which is known as vitil- 
igo or leucopathia acquisita. This oc- 
curs later in life, either as a sequela to 
certain well-known diseases (scarlet fever, 
typlius, recurrent fever), or as a symi)tom 
of an epidemic disease of unknown eti- 
ology (vitiligo endemica), or finally with- 
out any i-ecognizable cause. The forma- 
tion of white spots, within which the hairs 
are also white (lencotrichia acqidsita cir- 
cumscripta), takes place usually sj'mmet- 
ricallv, and mav extend over the greater 
Irap^^eSfviffrom^^^^^^ part of the body (Fig. 115). The white 




ABSENCE OF PIGMENT: CYST-FORMATION. 



251 



areas are surrounded by a border of more deeply pigmented skin ; and 
this suggests that with the disappearance of the pigment at one point the 
pigment is transferred to adjacent i)arts. The loss of color in the hairs 
(even as in old age) begins always in the root, no more pigment being 
transferred from the hair-papilla to the hair-bulb. Finally the pigment- 
cells of the papilla disaxDpear altogether. 

A third form of loss of pigment is associated with traumatic or infec- 
tious inflammations of the skin, particularly in syphilitic exanthemata 
and in leprosy ; this condition is known as leucoderma. 

In scars of the skin which remain white, the newly formed tissue 
replacing the defect does not possess the power of producing pigment ; 
and consequently represents a colorless cicatrix covered by epithelium. 
Not infrequently such a scar may be surrounded by a pigmented border. 
In mild forms of inflammation, in which the tissue of the skin suffers jio 
loss (syphilis), the disappearance of color may immediately follow the 
inflammation, or not until later, in which case there may occasionally 
occur a preceding stage of increased pigmentation. According to Ehr- 
mann the lack of pigment in such cases is to be explained either by the 
fact that no chromatophores are i)resent in the corium to furnish pigment 
to the epithelium, or the changed epithelium is not able to take up the 
pigment from the latter when present. The pigment which still remains 
in the cutis may then be absorbed. 

According to Muncli, vitiligo is of common occurrence in Turkestan, and is consid- 
ered by the natives (Sarts) to be contagious, so that they isolate the individuals affected 
with this disease and contine them with lepers in enclosed courts. It is probable that 
in the literature vitiligo endemica has been many times mistaken for lepra maculosa, 
and has been described under the designation " white leprosy of the Jews. " 

Literature. 

(^Absence of Pigment. ) 

Behrend: Canities (Poliosis). Eulenburg's Realencyklop., 1894 (Lit.). 
Beigel: Beitr. z. Gesch. d. Albinismus part. u. d. Vitiligo, Dresden, 1864. 
Ehrmann: Hautentfarbung durch syph. Exantheme. Arch. f. Derm., Ergzli., 1891. 
Jadassohn: Hautentfarbung. Vierteljahrsschr. f. Derm., 1880; Pigmentverschlep- 

pung. Arch. f. Derm., 1892. 
Landois: Plotzliches Ergrauen der Haupthaare. Virch. Arch., 35 Bd., 1866. 
Marc: Pathogenese der Vitiligo. Virch. Arch., 136 Bd., 1894. 
Munch: Lepra u. Vitiligo im Sliden Russlands, Kiew, 1884-86. 
Norris : An Extensive Case of Vitiligo. Univ. of Penn. Med. Bull., 1903. 
Schmorl: Pigment verschleppung. Cbl. f. allg. Path., v., 1894. 

XVI. The Formation of Cysts. 

§ 76. A cyst is a circumscribed cavity which is shut off from the sur- 
rounding tissues by a connective-tissue membrane or by tissue of a more 
complex structure, and possessing contents differing in nature from the 
capsule. Cysts may occur in any tissue. When composed of but a sin- 
gle chamber, the cyst is called a simple cyst ; when divided into a number 
of compartments, it is known as a multiloctdar cyst. 

The most common form is the so-called retention=cyst, which arises 
f rom the accumulation of secretions in preexisting spaces which are lined with 
epithelium or endothelium. 

In glands provided vs^ith an open duct, retention -cysts will be 
formed as the result of the obstruction of the duct, provided that actively- 



252 



THE RETROGRADE CHANGES. 




secretiDg epithelium still exists behind the point of obstruction. Such 
cysts are of frequent occurrence in the sebaceous glands, hair-follicles, 

uterine glands, mucous glands of the in- 
testinal tract, tubules of the epididymis 
(Fig. 116, c), urinary tubules (Fig. 74) ; 
less frequent in the biliary passages, 
in the breast, pancreas (Fig. 117, b), in 
the glands of the mouth, etc. Larger 
open canals, such as the ureters, vermi- 
form appendix, and tubes (Fig. 118, c), 
may also undergo cystic dilatation as the 
result of the collection of secretions. 
The obstruction of a given duct may 
be due to accumulation of secretion, to 
the formation of adhesions (Fig. 118, e), 
cicatricial obliteration, comj^ression, or 
constriction of its lumen. 

Closed glandular cavities and tubes, 
such as the follicles of the thyroid and 
the glandular tubes of the parovarium, 
may also become cystic when their walls 
produce an abnormal amount of secre- 
tion. Likewise, the remains of fetal 
passages and clefts, as, for example, re- 
mains of the branchial clefts, urachus, Miiller's ducts, etc., may also 
become cystic. 

Small cysts, such as those developing in mucous glands, vary in size 
from a millet seed to that of a pea. Larger cysts, such as occur in the 
liver and ovaries, may attain the size of a fist and even larger. 

The contents of cysts depend upon the nature of the tissue in which 
they are formed. Thus the cysts of the sebaceous glands and hair-folli- 
cles (atheroma) contain a pultaceous, white, or grayish-white, more rarely 
brown, mass, which consists essentially of squamous cells, in part show- 
ing cornification, and also of fat-globules and cholesterin. The cysts oc- 
curring in mucous glands contain a mucous fluid which is either clear, 
or white and cloudy, as the result of the presence of cellular elements. 




Fig. 116.— Section of the testicle and 
epididymis, with multiple cysts in the head 
of the epididymis, a. Testis; epididy- 
mis ; c, multilocular cysts. Slightly reduced. 




Fig. 117.— Pancreas cyst, due to dilatation of branches of Wirsunsy's duct, a. Gland-tissue; b, cysts; c, 
transverse section of artery ; d, longitudinal section of vein. Natural size. 

Hsemorrhage into a cyst from the cyst- wall gives a red or brown color to 
the contents. When great numbers of cells are present in the cyst- con- 
tents, this may become converted into a semi-solid fatty mass, which 



CYST-FORMATION. 



253 



may undergo calcification. Cysts of the thyroid and kidneys contain 
colloid masses, or a clear though occasionally cloudy fluid. 

Retention=cysts lined with endothelium may develop from blood- 
and lynq^h- vessels, lymph-spaces, bursse, and tendon-sheaths. Here also 
the content of the cyst is dependent upon its place and mode of origin. 

As retention -cysts increase in size the stretching of the cyst -wall 
would ultimately lead to a defect in the continuity of the wall if no new 
formation of tissue took place. Cyst formation is, therefore, not purely 
a degenerative process; such a new formation of tissue takes place first 
in the epithelial or endothelial lining of the cyst, but the connective- 
tissue elements of the wall also increase, so that in spite of the stretching 




Fig. 118.— Hydrops of the Fallopian tube, with perisalpinffitic and periovarian adhesions, a. Uterus ; 
b, uterine portion of the tube showing cystic dilatation and adhesions with the neighboring parts ; d, 
ovarium ; e, membranous adhesion. Two-thirds natural size. 

the wall of the cyst becomes no thinner, and under certain conditions 
may even increase in thickness. Moreover, cyst formation is often 
associated v^ith a pathological formation of new glandular tissue, 

and in this way constitutes a secondary change in hyi3ertrophic or tumor- 
like growths. It is, therefore, sometimes impossible to draw a sharp line 
between the simple cystic dilatations of preexisting gland-canals and 
gland-spaces, and those tumors, the cystomata, which are characterized 
by cyst formation (see Cystoma). Endothelial cysts may also develop out 
of newly formed lymph-spaces and lymph -vessels. 

A second form of cyst is the degeneration=cyst, which arises through 
the partial disintegration and liquefaction of a tissue. Cysts formed in 
this manner occur in the brain, hypertrophic thyroids, and in tumors. 
They may contain a clear or cloudy, or at times hsemorrhagic exudate. 

A third form of cysts results from the formation of a connective= 
tissue capsule around foreign bodies, which have found entrance to the 
tissues, as, for examx^le, about a bullet ; or also about necrotic areas, or 
haemorrhagic extravasates. 

A fourth variety of cysts is formed by parasites which pass through 



254 



THE RETROGRADE CHANGES. 



a cystic stage in the course of their development in the body, and [ire 
likewise surrounded by a connective -tissue capsule. 

Literature. 

{Retention- Cysts. ) 

Aschoflf: Cysten. Ergebnisse d. allg. Path., II. Jahrg., Wiesbaden, 1897 (Lit.). 
Bard, et Lemoine : De la maladie Ivj^stique essentielle des organes glandulaires, Paris, 
1690. 

Chiari: Genese der sog. Atheromcysten. Zeitschr. f. Heilk., xii., 1891. 
Franke: Blutcyste der seitliclien Halsgegend. Deut. Zeitschr. f. Chir., 28 Bd., 1888 
(Lit.). 

Hennes: Angeb. Aiiswiicbse am Halse. Arch. f. Kinderheilk., ix., 1888 (Lit.). 
Hess: Leber eine subcutane Flimmercyste. Beitr. v Ziegler, viii., 1890. 
Kiihne: Pathol. Histologic der Cystenbildimg. Virch. Arch., 158 Bd.. 1899. 
Marchand: Cysten. Eulenbnrg's Realencyklop., 1894 (Lit.). 
Nordmann: Galaktocele. Virch. Arch., 147 Bd., 1897. 

Philippson: Anatomische Untersuchungen ilber Nierencysten. Virch. Arch., Ill 
Bd.. 1888. 

V. Recklinghausen : Ueber die Ranula, die Cyste der Bartholin 'schen Drilse und die 

Flimmercyste der Leber. Virch. Arch., 84 Bd., 1881. 
Richard: Geschwiilste der Kiemenspalten. Beitr. v. Bruns, iii., 1888. 
Sabourin: La degenerescence kystique du foie et des reins. Arch, de phys., x,, 1882. 
Sasse: Cysten der Mamma. Arch. f. klin. Med., 54 Bd., 1897. 

Terburgh: Leber Leber- und Merencysten. Inaug.-Diss. v. Freiburg, Leiden, 1891. 
Torok: Entstehung der Atheromcysten. Monatsschr. f. prakt. Derm., xii. 
Virchow: Die krankhaften Geschwiilste, i., Berlin, 1863. 



CHAPTER VI. 



Hypertrophy and Regeneration. Results of Tissue- 
Transplantation. Metaplasia. 

I. General Considerations Concerning the Processes Known as 
Hypertrophy and Regeneration, and the Accompanying Cellular 
Changes. 

§ 77. In a general sense, hypertrophy is an increase in the size of a 
tissue or organ, due either to aii increase in the size or in the number of the in- 
dividual elements, in such a way that the structure of the hypertrophic 
tissue is like that of the nor- 
mal, or at least does not differ 
essentially from it. 

In a more limited sense hy- 
pertrophy is an increase in size 
due to an enlargement of the in- 
dividual elements alone ; the en- 
largement due to an increase in 
the number of the individual ele- 
ments being designated as hy- 
perplasia. 

Hypertrophy may result 
from morbid impulses inherent 
in the germinal cells, or from 
influences acting during the 
life of the individual. 

If an abnormal tissue-in- 
crease occurs during the period 
of embryonal development, or 
of extra-uterine growth, and if 
no influences are recognizable 
that would account for the in- 
creased growth, the condition 
may be explained as the result 
of a congenital predisposition, 
and may be designated as a 
hypertrophy due to a con= 
genital anlage. If the en- 
largement affects the entire body, for example, if a newly born child 
weighs 5-6 kgm., or if an individual should reach the height of 180-200 
cm., the condition is called a general giant growth. When the en- 
largement affects only individual parts of the body, as, for example, the 
entire head or one-half of it, or one extremity, or a finger, or the vulva, 
it is called a partial giant growth. The giant growth of several parts 
of one side of the body is designated a half giant growth ; one involving 




Fig. 119.— Elephantiasis lemorum neuromatosa. 



256 



THE PROGRESSIVE CHANGES. 



all the body -parts Is very rare. Hypertrophic growths of the skin and 
subcutaneous tissues, leading to a disfigurement suggesting the appear- 
ance of the skin of the pachydermata, 
are known as elephantiasis (Figs. 119, 
120). 

In hypertrophic growth of an ex- 
tremity or of a finger all the elements 
of the same are uniformly enlarged. 
In elephantiasis of the extremities the 
connective tissue of the skin and sub- 
cutaneous structures is especially likely 
to become increased; but the develop- 
ment and structure of these growths 
vary greatly. In one case all the con- 
nective-tissue elements may be uniform- 
ly increased, in another case only indi- 
vidual elements; as, for example, the 
connective tissue of the nerves, blood- 
or lymph-vessels ; or at least, the path- 
ological new-formation takes its start 
from these. It is therefore possible to 
distinguish different forms of elephan- 
tiasis according to the structure of the 
hypertrophic part: elephantiasis neuro- 
matosa (Fig. 119), angiomatosa, lymphan- 
giectatica (Fig. 120), lipomatosa, fibrosa, 
etc. 

If, as a result of some peculiar pre- 
disposition of the skin, there occurs a 
hypertrophy of the horny layer of the 
epidermis (Fig. 121, c), so that the skin 
becomes covered with horny plates, scales, or even with spines, the 
condition is designated ichthyosis. 




Fig. 120.— Elephantiasis cruris lymphan 
glectatica. 



c 6' 



Fig. 121,— Ichthyosis congenita. Section through the skin of the trunt of the body (alcohol, plcrocar- 
mine.) a. Cerium, with glands ; b, papillary body, with rete Malpighii ; c, hypertrophic horny layer of 
the epidermis ; c7, dilated hair-follicles, lined with horny epithelium ; e, hairs. X 40. 



HYPERTROPHY AND HYPERPLASIA. 



257 



This change may be present even at birth {ichthyosis congenita) ; and 
the new-born child (Fig. 122) may be wholly covered with hard horny 
plates, which have been split open at different points as the result of the 
growth of the underlying tissues. 
The pathological cornification af- 
fects chiefly the surface (Fig. 121, 
c), but may extend also into the 
hair-follicles (Fig. 121, d). 

In other cases, at a later period 
of development, as during the first 
years of life, localized thickenings 
of the horny layer may develop, 
consisting of either small scales or 
plates, or larger ones, giving the 
skin a rough and checkered ap- 
pearance. The corium and the 
papillae are usually not involved in 
the ichthyosis ; but occasionally the 
papillary bodies may be hypertro- 
phic and enlarged, thus increasing 
the rough and nodular appearance 
of the surface {ichthyosis hystrix). 
When the excessive cornification 
is sharply limited to areas of small 
size, there are formed circum- 
scribed warts with rough, epithelial 
covering, which are known as ich- 
thyotic warts. In rare cases there 
may be developed a more exten- 
sive horny layer over the hyper- 
trophic papillae, whose scales are 
arranged at right angles to the 
surface of the skin ; and these oc- 
casionally may attain to such size 
that they are called cutaneous 
horns (Figs. 123, 124). 

The hypertrophic development of hair over those parts of the body 
where only downy hair, or even no hair at all, should be found is known 
as hypertrichosis. Such an abnormal hairiness may cover a larger or 

smaller area of the body, 
and depends either upon 
a persistence and abnor- 
mal development of the 
lanugo (hypertrichosis 
lanuginosa foetalis) (Fig. 
125), or upon a patholo- 
gical development of the 
secondary hairs. An ex- 
cessive growth of the nails 




Fig. 133.— Ichthyosis congenita. 




r 



Fig. 133.— Cornu cutaneum, 
from back of hand. (Natural 
size.) 



Fig. 134.— Cornu cutaneum, 
from arm. (Natural size.) 



leads to the condition 
known as hyperonychia, 
which is often followed by a claw-like deformity of the same desig- 
nated onychogryphosis. It is to be noted, however, that the patholog- 
ical over-growths of the nails are usually acquired. 



258 



THE PROGRESSIVE CHANGES. 



Next to the enlargements associated with general or partial giantism 
the bones most frequently undergo a form of hypertrophy corresponding 
to the congenital elephantiasis of the skin. The head is usually affected, 
the bones of which may undergo a very marked enlargement (Fig. 126), 
leading to a deformity in which the patient's head comes to resemble that 
of a lion, hence the name leontiasis ossea. Further, there often develop 
upon the skull or other bones of the body circumscribed bony growths 
known as exostoses, which are inherited and not dependent upon extrin- 
sic influences. 

In the internal organs hypertrophic processes dependent purely upon 
intrinsic causes are rare; but the brain, for example, may reach an 
abnormal size. 

It cannot always be definitely stated to what extent hypertrophy of 
the tissues is to be attributed to a 




Fig. 135.— Head of a hairy individual, a woman. Fig. 126.— Leontiasis ossea, occurring in a boy af- 

(After Hebra.) fected with general giant-growth. (Observed by 

von Biihl.) 



intrinsic causes. For example, cutaneous horns and elephantiasis -like 
thickenings of the skin may develop as the result of inflammation. 

In general, the early appearance of a hypertrophic growth, the 
hereditary nature of the pathological peculiarity, and the absence of any 
external etiological factor, speak for the congenital nature of the condi- 
tion. The fact that later influences may apparently cause the growth 
does not preclude the existence of a congenital predisposition. Thus the 
excessive bony growths of the head above mentioned may follow trauma 
or acute inflammations. External influences may therefore be the excit- 
ing cause of the proliferation, but not the primary cause of the same ; 
since we know by experience that the given injurious influences are able 
to produce such changes only in tissues possessing a special predisposi- 
tion. 

Not infrequently an abnormal tendency to excessive growth may show 



TISSUE-HYPERTROPHIES OF CONGENITAL ORIGIN. 



259 



itself iu a })remature development of certain organs, the structure remaining 
normal. The external and internal sexual organs are most frequently 
affected. Girls, even in the first years of life, may show a development 
of breasts and external genitals and a growth of hair corresponding to 
that of the sexually ripe woman ; and menstruation may be established 
at this early period. 

The size of the entire body as well as of its separate parts and organs shows con- 
siderable variation within physiological limits, according to the race, family, and indi- 
vidual. The variation in the relation of the size of single parts and organs to that of 
the entire body is less marked. 

The average height of the body in well-built individuals is, according to Vierordt 
("Daten u. Tabellen fiir Med.," Jena, 1893), as follows: Men 172 cm., women 160 cm. ; 
of the new-born, males 47.4 cm., females 46.75 cm. The average body-weight in 
Europe is for men about 65 kgm., that of women about 55 kgm., that of the new-born 
about 3,250 gm. 

The average weight of the internal organs is as follows, the figures in parentheses 
being for the new-born: Brain 1,397 (385) gm., heart 304 (24) gm., lungs 1,172 (58) gm., 
liver 1,612 (118) gm., spleen 201 (11.1) gm., right kidney 131, left kidney 150 gm., both 
kidneys 299 (23.6) gm., testicles 48 (0.8) gm., muscles 29,880 (625) gm., skeleton 11,560 
(445) gm. Expressed in percentages of the body-weight the figures for adults and new- 
born are (the latter in parentheses): Heart 0.52 (0.89), kidneys 0.48 (0.88), lungs 2.01 
(2.16), stomach and intestines 2.34 (2.53), spleen 0.346 (0.41), liver 2.77 (4.30), brain 2.37 
(14.34), adrenals 0.014 (0.31), thymus 0.0086 (0.54), skeleton 15.35 (16.17), muscles 43.09 
(23.4). 

Literature. 

{Tissue- Hypertrophy of Congenital Origin.) 

Arnheim: Congen. halbseitige Hypertrophic. Virch. Arch., 154 Bd., 1898 (Lit,). 
Baas: Das Hornhauthorn. Cbl. f. allg. Path., viii., 1897. 

Bartels: Abnorme Beliaarung. Zeit. f, Ethnol., viii., 1896; Affenmenschen, ib., xvi., 
1884. 

Behrend: Hypertrichosis. Eulenburg's Realencyklop., 1896 (Lit.). 
Brandt: Hundemenschen. Biol. Cbl., xvii., 1897. 

Bruns: Ueber Ilankenneurom. Virch. Arch., 50 Bd. ; Beitr. z. klin. Chir., 1891. 
Busch.: Riesenwuchs der Extremitaten. Arch. f. klin. Chir., vii., 1866. 
Carbone: Ictiosi congenita. Arch, per le Sc. Med., xv., 1892. 
Caspary: Ichthyosis congenita. Vierteljahrsschr. f. Derm., xiii., 1886. 
Chiari: Ueber Hypertrichosis. Prag. med. Woch., 1890. 

Demme: Halbs. Muskelhypertrophie. 27. Jahresber. d. Jenner'schen Kinderspitals, 
Bern, 1890. 

Ecker: Ueber abnorme Beliaarung des Menschen, Braunschweig, 1878. 
Esmarch u. Kulenkampff : Die elephantiastischen Formen, Hamburg, 1885. 
Esoff: Ichthyosis. Virch. Arch., 69 Bd., 1877. 
Ewald: Hypertrophic der Hand. Virch. Arch., 56 Bd., 1872. 
Fischer: Riesenwuchs der Extremitaten. Deut. Zeitschr. f. Chir., xii., 1880. 
Friedrich: Halbseitige congenitale Kopfhypertrophie. Virch. Arch., 28 Bd., 1863. 
Hornstein: Halbseitiger Riesenwuchs. Virch. Arch., 133 Bd., 1893. 
Hiirthle u. Nauwerck : Fibroma mollusc, u. congen. Elephantiasis. Beitr. v. Ziegler, 
i., 1886. 

Jacobson: Universeller Riesenwuchs. Virch. Arch., 139 Bd., 1895. 
Jordan: Pathol. -anat. Beitr. z. Elephantiasis congenita. Beitr. v. Ziegler, iii., 1890. 
KiwuU: Zur Casuistik der lialbseitigen Gesichtsliypertrophie. Fortschr. d. Med., 
viii., 1890. 

Klein: Pubertas praecox. Deut. med. Woch., 1899. 
Kussmaul: Geschlechtliche Friihreife. Wiirzb. med. Zeitschr., 1862. 
Mitwalsky : Hauthorner der Augenadnexa. Arch. f. Derm., 27 Bd.,1894. 
Nonne: Elephantiasis congenita hereditaria. Virch. Arch., 125 Bd., 1891. 
Poisson: Hyperostose diffuse des maxillaires superieures. Sem. med., 1890. 
Poumayrac: fit. sur 1 'hypertrichosis, Bordeaux, 1893. 
V. Recklinghausen: Die multiplen Fibrome der Haut, Berlin, 1882. 
R6na: Ichthyosis im Jiinglingsalter. Arch. f. Derm., xxi., 1889. 
Spietschka: Ueber Elephantiasis congenita. Arch. f. Derm., xxiii., 1891. 
Trelat et Monod: De 1' hypertrophic unilaterale. Arch. gen. de med., 1869 
15 



260 



THE PROGRESSIVE CHANGES. 



TJnna: Keratoma palmare et plant, congen. Vierteljahrssclir.-f. Derm., x., 1883. 
Virchow: Handbucli der spec. Pathol., i., 1854; Die krankbaften Geschwiilste, 1865. 
Wiedersheim : Der Bau des Mensclien, Freiburg, 1898. 

§ 78. The hypertrophies of the tissues due wholly to extrinsic 
influences without the aid of a congenital predisposition owe their 
origin either to au increase in the activity of the tissue, to diminished 
use, defective retrograde change, or finally to prolonged or frequently 
repeated mechanical, chemical, and infectious irritations of the tissues. 
Under certain conditions the removal of pressure may also give rise to a 
localized hypertrophy. 

Hypertrophy from overwork is most frequently observed in the case 
of muscles and glands, but may occur also in other tissues. If the heart is 
called upon to do an extra amount of work as the result of diseased con- 




FiG. 127.— Transverse section of a heai'i showing hypenropliy of the left venincle, resulting from aortic 
stenosis and insufficiency, o, Left, b, the right ventricle. Reduced iV. 

ditions of the vah^es, aorta, or kidneys, and if such conditions exist for 
some time, that part of the heart-muscle upon which the extra work falls 
suffers a more or less pronounced hypertrophy (Fig. 127), so that as a 
result the mass of the heart may reach double that of the normal or even 
more. 

In a similar manner the striated muscles, and the unstriped muscle of the 
Madder, ureters, uterus, intestine, and blood-vessels may become hypertrophic 
as the result of persistent increase in their activity. 

As the result of an increase of the supporting strain from whatever 
cause the bones may become thickened, and the bony trabeculse of the 
medullary portion become increased in size. 

Of the glands, the Mdneys, and liver in particular are able to change 
their size according to the functional demands, and may consequently 
present a marked hypertrophy. Should one kidney be destroyed the 
remaining one may become so enlarged that it may reach approximately 



ACQUIRED HYPERTROPHY. 



261 



the same weight that the two kidneys together originally possessed. 
Likewise the liver after a destruction of a part of its parenchyma 
through disease may make good its loss by a hypertrophy of the remain- 



ing 




Fig. 138.— Hypertrophy of an incisor 
tooth of a white rat, the result of an 
oblique position of the jaw. (Natural 
size.) 



tissue. Since in this way a compensation for the defect and a 
restoration of the normal function is brought 
about, such a tissue-increase may be ap- 
propriately designated compensatory hy= 
pertroph)^ The same term may also be 
applied to muscle -hypertrophy, if through 
it functional disturbances are compensated. 
A similar compensatory hypertrophy is said 
to occur also in the case of adrenal tissue. 
In the case of other glands, such as the 
salivary glands, ovaries, testicles, and mam- 
mary glands, such a compensatory hyper- 
trophy either does not occur at all, or takes place only during the 
period of development. The loss of an ovary or testis in adult life can 
hardly result in an increased activity or hypertrophy of the remaining 
organ. Extirpation of the larger part of the thyroid gland is not fol- 
lowed by any pronounced hypertrophy of the 
remaining portion ; but, on the other hand, the 
hypophysis undergoes an enlargement which 
must be regarded as compensatory. In the 
case of the lungs, an increase in the activity of 
one portion after the loss of other parts re- 
sults usually in a permanent over distention 
which may lead eventually to atrophy. On 
the other hand, if during embryonic life a de- 
fective development of one lung takes place, 
the other lung may undergo a compensatory 
growth, which in the case of total agenesia of 
one lung may reach a very pronounced degree. 
For the other organs the general princix)le 
may be applied that compensatory hypertro- 
phy is the more perfect the younger the indi- 
vidual. In the case of the brain a compen- 
satory growth of one part after the loss of 
another is possible only during the early stages 
of development. 

Hypertrophy from lessened use occurs in 
the case of tissues which are subjected to a 
constant use. Thus, for example, a dimin- 
ished desquamation of the horny layer of the 
epidermis leads to its pathological thickening. 
If, as the result of the destruction of an op- 
posing tooth or an oblique position of the 
teeth, the incisor teeth in rodents are not 
worn down by use, they may grow out into 
long and curved tusks (Fig. 128). Likewise 
the finger- and toe-nails may reach an ab- 
normal siae either from lack of wear or from 
being left uncut. Hypertrophy due to de= 
fective retrograde change occurs in organs 




Fig. l™'y.— Elephatiiisis .scroti in a 
Samoan nineteen years of age. (Af- 
ter Uthemann, Deutsche metl. Wo- 
chenschr., 1895.) 



which after 



period of physiological growth undergo a diminution in size. 



definite, 
For ex- 



262 



THE PROGRESSIVE CHANGES. 



ample, the uterus after pregnancy may remain abnormally large as the 
result of a failure of involution. The thymus gland, which should begin 
to atrophy after the tenth j^ear of life, may jDersist for a much longer 
period than normally. In bones whose configuration has been brought 

about under the influence of 
the surroundings by means 
of an alternation of build- 
ing-up and tearing-down, a 
lessening of pressure may 
be followed by hypertrophy. 
In idiots whose brains are 
deficient in size there is very 
often seen a hj^Dcrostosis of 
the inner surface of the base 
of the skull (Chiari). A 
unilateral hyperostosis of 
the skull is associated with . 
a unilateral hypoplasia of 
the brain. 

Frequently repeated or 
long=protracted mechani= 
cal, thermal, chemical, or 
infectious irritations give 
rise to proliferative proc- 
esses leading to tissue-hy- 
pertrophies, which accord- 
ing to their etiology and 
course must be regarded as 
chronic inflammations; and 
such new-formations of tissue 
may therefore be regarded as 
an inflammatory tissue=hy= 

Fig. 180.— Acromegaly, according to Erb and Arnold. (Osteo- pertrophy. They are char- 
arthropathy, according to Marie and Souza-Leite.) actcrized very of tCU by the 

fact that, in the enlargement 
of the organ, not all of its parts are equally involved in the hypertrophy ; 
but certain individual elements, usually the connective tissue, occasion- 
ally also the epithelium, undergo hyperti'ophy to an especial degree, so 
that the structure of the organ (skin, gland, etc.) is no longer wholly 
typical. 

If the skin is frequently subjected to mechanical irritation and press- 
ure, as, for example, the toes through an ill-fitting boot, there may arise 
in consequence thickenings of the horny layer of the epidermis, known 
as callus or corn (clavus). Prolonged irritation of the skin in the neigh- 
borhood of the genital openings, caused by gonorrhoea! discharges, may 
cause a marked elongation and branching of the papillae with an accom- 
panying thickening of the epithelium, leading to the formation of the 
warty, cauliflower-like growths known as venereal tcarts or condylomata 
acuminata. Chronic inflammations of the corium and subcutaneous tis- 
sue, due to infection or to animal parasites (Filaria Bancrofti), not infre- 
quently give rise to extensive fibrous hypertroi)hies of the tissue known 
as elephantiasis (Fig. 129). Such elephantiasic hypertrophies of the tissue 
may attain extraordinary proportions. In a similar manner there may 
occur in the bones, as the result of chronic infectious processes (syphilis, 





ACQUIRED HYPERTROPHY. 



263 



for example), extensive hypertrophies characterized by an increased 
formation of bone-substance. 

In the majority of cases of those tissue-hypertrophies which appear 
during the course of life as acquired formations caused by external influ- 
ences, the causa efficiens may be recognized with more or less certainty ; 
but there are also many cases in which, at the present time, this is either 
wholly impossible or possible only to a limited extent. For example, 
there occur enlargements of the spleen, and of the lymphadenoid tissue of the 
lymi:)h-giands and of the lymph-nodes in the mucous membranes, which 
are of the nature of hy]3ertrophies, whose causes we are unable to recog- 
nize. Very imperfect, also, is our knowledge concerning the etiology of 
the enlargements of the distal portions of the extremities (Fig. 130), resem- 
bling partial giant-growth, which have been described as acromegaly 
(Marie), pachyakria (von Eecklinghausen), and osteoarthropathie hyper- 
trophiante (Marie). In a part of these cases there are an associated en- 
largement of the bones of the face and deformities of the spinal column. 
These changes appear usually in youth or middle age, rarely in old age, 
and show a gradual development. 

So far as anatomical investigations (Arnold, Marie, Marinesco, 
Thomson, Holsti) have been able to throw light upon this question, the 
pathological change consists in an increase of all the tissues of the termi- 
nal portions of the extremities and of the face, in particular of the bony 
parts, in that the bones become thicker (Fig. 131) and at the same time 
become the seat of rounded or i)ointed exostoses. On the other hand, an 
increase in the length of the bones has not yet been demonstrated with 




Fig. 131.— Skeleton of the hand, with hypertrophic bones, from the case of acromegaly pictured in Fig. 130. 

(After Arnold.) 



certainty in this disease (von Eecklinghausen, Arnold), and so the desig- 
nation pachyakria given by von Eecklinghausen is well chosen. 

The cause and nature of these pathological phenomena are as yet 
obscure ; and the terms mentioned above are not used by all authors with 
the same meaning. In Germany the designation acromegaly is applied 
to all forms of enlargement of the ends of the extremities which lead to 



264 



THE PROGRESSIVE CHANGES. 



a paw -shaped deformity of the hands aud a gigantesqne appearance of 
the feet, while Marie, who first described these conditions, attempts to 
draw a sharp line between acromegaly and osteoarthroj)athie hypertro- 
phiante. He holds that in acromegaly the hands and feet are not de- 
formed, but are symmetrically enlarged, the thickening and broadening 
diminishing toward the tips of the extremities, so that the terminal 
l^halanges of the fingers and toes are but slightly thickened, while, on the 
other hand, in osteoarthropathie hyj)ertrophiante the terminal phalanges 
are enlarged so as to resemble drumsticks, and the articular ends of the 
bones are irregularly thickened. In the first affection the lower jaw is 
lengthened, in the latter it is thickened. Marie believes that in many 
cases osteoarthropathie hj pertrophiante is a sequela of inflammatory 
affections of the lungs and pleurae, and designates the condition accord- 
ingly as osteoarthropathie hypertrophiante pneumique, and holds that 
the connection between these processes is to be found in the taking up 
into the body -fluids of j)oisonous products from the inflammatory foci in 
the lungs, so that the affection of the bones is to be regarded as an infec- 
tious toxic hypertrox^hic inflammation. 

By other authors the causes of acromegaly and osteoarthropathie hy- 
pertrophiante are to be sought in a congenital predisposition (Virchow), 
in disturbances of the sexual function (Freund), in a hyj)ertrophy of the 
hypophysis (Henrot, Klebs), in persistence of the thymus (Erb, Klebs), or 
in nervous influences (von Recklinghausen) ; but none of these hj pothe- 
ses is adequately su^Dported by anatomical and clinical observations. 
From the investigations made up to the j) resent time it follows rather 
that these conditions do not represent an excessive growth similar in 
nature to a partial giant growth, but are acquired diseased conditions, 
which develop either as independent diseases- (acromegalj^ x^^^l^y^^i'i^^)? 
or as secondary j^henomena in the course of other diseases (osteoarthro- 
pathie hypertrophiante pneumique). 

The cause of the hypertrophic condition of the thyroid gland, occur- 
ring so frequently in many regions, is wholly unknown. 

Literature. 

(Compensatory Hypertropliy of Glands and of the Heart.) 

Beresowsky: Compensatorische Hypertrophie d. Scbilddruse. Beitr. v. Ziegler, xii., 
1892. 

Bizzozero: Accrescimento e rif^enerazione nell' organismo. Arch. p. le Sc. Med., 
xviii., 1894. 

Bostrom: Beitr. z. path. Anat. d. Nierc, Freiburg, 1884. 
Bozzi: Untersiich. iiber die Schilddriise. Beitr. v. Ziegler, xviii., 1895. 
Eckhardt: Compeusat. Hypertrophie der Meren. Virch. Arch., 114 Bd., 1888. 
Grawitz w. Israel: As above, ib., 77 Bd., 1879. 

Hodenpyl : Apparent Absence of the Spleen with General Compensatory Lymphatic 

Hyperplasia. Med. Rec, 1898. 
Horwatb.: Die Hypertrophie des Herzens, Wien, 1897. 
Krahe: Comp. Hyp. d. Speicheldrlisen. Inaiig.-Diss., Bonn., 1888. 
Leich.tenstern : Comp. Eierenhypertrophie. Berl. klin. Woch., 1881. 
Nothnagel: Ueber Anpassungen ii. Aiisgleichimgen bei pathologischen Zustiinden. 

Zeitschr. f. klin. Med., x., 1885; xi., 1886; xv., 1888. 
Perl: Comp. Nierenhypertrophie. Virch. Arch., 56 Bd., 1872.- 

Podwyssozky : Exp. Unters. lib. die Regeneration d. Drusengewebe. Beitr. v. 
Zieoier, i., 1886. 

Ponfick: Ziir Pathologic der Leber. Virch. Arch., 118, 119, and 138 Ed., 1889-1894. 
V. Recklinghausen: Pathologic des Kreislaufes u. d. Ernahrung, Stuttgart, 1887. 
Ribbert: Comp. Nierenhypertrophie. Virch. Arch., 88 Bd. ; Compens. Hypertr. d. 



REGENERATION. 



265 



Geschleclitsdrasen, ib., 120 Bd., 1890; Compens. Hypertrophie u. Regen. Arch. f. 
Entwickelungsmechan,, i., 1894. 
Hogowitsch; Verand. d. Hypopliyse nacli Entfernung d. Schilddriise. Beitr. v. 
Ziegler, iv., 1889. 

Sacerdotti; Ipertiolia compens. dei reni. Arch, per le Sc. Med., xx. ; Virch. Arch., 
146 Bd., 1896. 

Schuchardt : Compensat. Hypertrophie d. rechten Lunge. Virch. Arch., 101 Bd., 
1885. 

Stieda : Verhalten d. Hypophyse nach Entfernung d. Schilddriise. Beitr. v. Ziegler, 
vii., 1890. 

Stilling-: Compensat. Hypertrophie der Nebennieren. Virch. Arch., 118 Bd., 1899. 
Simmonis: Compensat. Hypertrophie d. Nebennieren. Virch. Arch., 153 Bd., 1898. 
Tang-l: Ueb. d. Hypertrophie u. d. phys. Wachstlium des Herzens. Virch. Arch., 116 
Bd., 1889. 

Velisch: Compens. Hypertrophie d. Nebennieren. Virch. Arch., 154 Bd., 1898. 
Wollmann: Ein Fall von Agenesie der 1. Lunge. Inaug.-Diss. , Freiburg, 1891. 
Ziegler: Ursachen d. pathol. Gewebsneubildungen. Intern. Beitr., Festschr. f. Vir- 
chow, ii., 1891. 

Zielonko: Stud. lib. die Hypertrophic des Herzens. Virch. Arch., 62 Bd., 1865. 

{Acromegaly, Pachyakria, Osteoarthropathie Kypertrophiante, and Hyper - 

trophy of the Skull. ) 

Arnold: Akromegalie, Pachyakrie oder Ostitis. Beitr. v. Ziegler, x., 1891; Beitr. zur 

Akromegaliefrage. Virch. Arch., 135 Bd., 1893. 
Bamberger: Knoclien verand. bei chron. Luugen- u. Herzkrankh. Zeit. f. kl. Med., 

xviii., 1890. 

Brooks: Acromegaly. Archives of Neurolog}', New York, i., 1898. 
Chiari: Basale Schildelhyperostose bei Idioten. Verh. d. path. Ges., ii., Berlin, 1900. 
Erb: Ueber Akromegahe. Deut. Arch. f. kl. Med., 42 Bd., 1888. 
Freund: Ueber Akromegalie. Samml. klin. Vortr., jSTos. 329-30, Leipzig, 1889. 
Friedreich: Hyperostose des gesammten Skeletes. Virch. Arch., 43 Bd., 1863. 
Fritsche u. Klebs: Ein Beitrag zur Pathologic des Riesenwuchses, Leipzig, 1884. 
Holsti: Akromegalie avec autopsie. Festkrift fr. Pathol. Anatom. Institutet Helsing- 
fors, 1890. 

Lefebvre: Des deformat. osteoarticulaires consec. a des mal. de Lapp, pleuropulmo- 
naire, Paris, 1891. 

Marie : Sur deux cas d'akromegalie, hypertrophic singuliere non congenitale des ex- 
tremites et cephalique. Rev. denied., vi., 1886; De I'osteoarthropathie hjqiertro- 
phiante pneumique. Ib., x., 1890. 

Marie et Marines CO : Sur I'anatomie pathol. de I'akromegalie. Arch, de med. exp., 
iii., 1891. 

Minkowski: Ueber eincn Fall von Akromegalie. Berl. klin. Woch., 1887. 
Oestreich: Riesenwuchs imd Zirbeldriisengescliwulst. Virch. Arch., 157 Bd., 1899. 
Rauzier: Osteoarthropathie hypertrophiaute d'origine pneumique. Rev. de med., 
xi., 1891. 

V. Recklinghausen : Ueber Akromegalie. Virch. Arch., 119 Bd., 1890. 

Schtitte: Path. Auat. u. Aetiol. d. Akromegalie. Cbl. f. allg. Path., ix., 1898 (Lit.). 

Souza-Leite: De Fakromegalie, Paris, 1890. 

Spillmann et Haushalter: Osteoarthropathie hypertrophiaute. Rev. de med., x., 

1890. 

Sternberg: Die Akromegalie, Wien, 1897. 

V. Striimpell: Zur Pathologic d. Akromegalie. Deut. Zeit. f. Nervenheilk., xi., 1897. 
Thomson: Acromegaly with the Description of a Skeleton. Journ. of Auat. xxiv., 
1891. 

Verstraeten: L'akromegalie. Rev. denied., ix., 1889. 

Virchow. Ueber Akromegalie. Berl. klin. Woch. and Deut. med. Woe]]., 1889. 

§ 79. Regeneration i^t^i^t process through ivhich tissues tvMch have been 
destroyed are restored. Under especial couditious this restoration may be 
brought abont by an enlargement of existing parts of cells (regeneration 
of axis-cylinders), but it is usually the result of new -formation of cells, ivhich 
arise in all cases through the division of preexisting cells. 

Eegeneration presupposes that the injured tissue is capable of pro= 
liferation, and is, moreover, a i:>henomenon which is in all cases depend- 



266 



THE PROGRESSIVE CHANGES. 



eut iipou extrinsic causes. In the fully developed organisin in which 
the different tissues and organs have reached their ultimate differentia- 
tion, each tissue ecoi produee onli/ iieir tissue of its own liiul. The spec= 
ificity of the tissues is of so decided a nature that epithelial cells 
can never gi\ e rise to connective tissue, nor can the latter ever produce 
epithelium. Even the individual varieties of epithelium cannot pass 
over into other types; the ectodermal cells cannot produce intestinal 
epithelium ; kidney epithelium can produce only cells having the charac- 
ter of kidney epithelinm, bnt never liver-cells or those of mucous glands, 
or coiiiuH^t i^■e tissue. Muscle-tissue can arise only from muscle-cells. 
^s"er^ es arid neuroglia can never arise from connective tissue. Only cells 
which are very closely related to each other can arise from tlie same 
parent-tissue or pass into each other. Thus the connective tissne of the 
periosteum can produce either ordinary connective tissue, cartilage, or 
bone — that is, tissues which are closely related to each othei', and which 
may be regarded as diff'erent modifications of the connective-tissue sub- 
stance. This power of producing different varieties of connective tissue 
is, however, not a property of all forms of connective tissue, but is con- 
fined, with a few exceptions, to those portions of the connective tissue of 



#1 J 



d 



:i 

Fig. 1o2.— The skin-portion of a laimrotoiuy wuuiul sixteen days old (Miiller"s fluid. Van Gieson's). 
«, Epithelium, Z), coriuui ; c, subcutaneous adipose tissue ; d, scar in corium ; i\ new epithelium; /. scar 
In adipose tissue. X 38. 

the skeleton which are capable of proliferation, and to the cartilaginous 
framework of the bronchi. 

In tissue (I(feels iu u'JiieJt oiih/ si)i(^le eeJls are lost (as, for exanixile, in the 
loss of single connective-tissue cells), or in the case of a move extensive 
destruction of cells without an interruption in the continuity of the connective 



REGENERATION AND REPAIR. 



267 



tissue of the Mood-vessels (as the loss of localized areas of the surface epi- 
thelium, or a group of glaud cells or of pulmonary epithelium), a com=> 
piete regeneration, a restitutio ad integrum, may take place, and the 
tissue be restored to a condition corresponding in all respects to that 
existing before the injury. After all injuries in ivliich the continuity of the 




Fig. 133.— Healing ulcer of the small intestine, with formation of new o-land-tiihes in the proliferating 
submucosa (Miiller's fluid, hoematoxylin). o, Mucosa; ij, submucosa ; c, c?, niuscularis: c, serosa ; /, re- 
mains of the floor of the ulcer not yet covered over with epithelium ; y, overhanging edge of the ulcer; 7i, 
portion of floor of ulcer covered with epithelium ; i, newly formed glands in the submucosa ; 7f, deep crypt 
lined with epithelium. X 18. 



mesoderynal supporting tissue is hroJcen, either with or without an associated 
injury to tissues of euto- and ectodermal origin, the regeneration is 
incomplete ; in that, at the point of injury there is formed a tissue 
which dei)arts more or less from the normal structure of the affected 
part, and shows a more or less marked loss of functional capacity as 
compared to the normal tissue. In g-eneral this tissue is a new formation 
of connective tissue, designated as a scar (Fig. 132, d) or cicatricial tissue, 
in individual organs (as in the heart -muscle) also called a calJositij, the 
new connective tissue resembling other formations of connective tissue, 
but not wholly identical with them. In the course of time it comes 
through a gradual change more and more to resemble normal tissue. 
Defects of the skeleton are replaced by scar-tissue which arises from the 
periosteum and bone-marrow, and by virtue of the peculiar properties of 
these tissues there develops a new-formation of hone-tissue within such 
scars, the structui-e coming to resemble closely that of normal bone. 

In many cases the cicatricial tissue consists purely of vascularized con- 
nective tissue (Fig. 132, d), which later becomes enriched only through 
the in-growth of nerve-fbres and the gradual development of elastic fibres. 
Scars bordering upon ectodermal or entodermal tissue may become cov- 
ered by a new-formation of epithelium (Fig. 132, e). Occasionally the 
structure of cicatricial tissue may undergo a further develoiDment, in 
that specific tissue formations either grow into it secondarily or preserved 
in it as remains of preexisting structures. The first i)rocess occurs most 
frequently in scars of the mucous membrane of the intestine (Fig. 133), 
and of glands in the neighborhood of their excretory ducts, and in scars 
of muscle (Fig. 134). In defects of mucous membranes which are 



268 



THE PROGRESSIVE CHANGES. 




replaced by scars formed tlirongh tlie proliferation of connective tissue 
(Fig. 133, h, f), the surface is first covered with epithelium {g, h, k), 

later there develop epithelial in- 
growths which bear the character 
of tubular glands (i). Gland-ducts 
(bile -ducts, ducts of the salivary 
glands) may grow into the develop- 
ing scar-tissue, and form new tubes 
or only solid cords of cells. Such 
a new-formation of gland-ducts 
may occur not only in the neigh- 
borhood of traumatic injuries, but 
also in the course of hsematogenous 
inflammations of the glands in 
question. 

A new-formation of gland-tissue 
proper in the neighborhood of 
scars is, on the other hand, want- 
ing in the case of the majority of 
I^IM'I-'I 4''»ni*^ljwi'-'v''VCT'* glands (liver, kidneys, testicles, 
I'^iy^'l'ii 'I? ^* 1 ovaries, thyroid, mammary glands, 

M>'J/«5!|)|^f i-'^ and lungs). Only in the case of 

salivary glands does the de- 
> '^'<'if,:Mi;T:'i >\''^\ . f . ujii velopment of the newly formed 

ducts lead to the formation of 
gland-lobules. 

In muscle-scars (Fig. 134) new 
muscle -fibres (d) grow from the 
ends of the old ones (a), and -pen- 
etrate into the scar -tissue, so that 
the scar becomes gradually re- 
placed by muscle. 

The preservation of remains of 
specific tissue-elements in the area 
; ' of cicatrization may be observed 

" in the case of both muscles and 

glands, especially in the periphery 
of traumatic injuries and anaemic 
necroses (Fig. 135), and in most 
cases also in infectious foci of dis- 
ease. The preserved gland -remains 
ll'V ! ? ! ; within the scar usually pi'esent an 

, ' atrophic condition (Fig. 135, h), 

i but islands of normal tissue (d ) 

j' may also be enclosed, and there 

1^ arises the possibility that such may 
undergo a compensatory growth. 
^ In inflammatory j)i'Ocesses in 

glandular organs which are char- 
acterized on the one hand by the 
destruction of the specific paren- 
chyma, and on the other by a new- 
formation of connective tissue having the character of scar-tissue, there 
are often seen in the diseased area new -formations of scar- tissue con- 



Fig. 134.— Soar of muscle and tendon, thirty-two 
days old (Flemming's solution. Van Glesou's). a. 
Old muscle ; Z), tendon ; c, scar ; d, newly formed 
muscle-fibres. X 100. 



REGENERATION ANT) REPAIR. 



269 



taining atrophic remains of the gland-tissue, and between these, islands 
of uninjured gland -tissue in a condition of hypertrophy. 

The mass of the scar is only rarely equal to the mass of the tissue 
lost, and there persists after the loss of considerable amount of tissue a 
more or less marked tissue defect. Over circumscribed areas of the 
surface of the skin, mucous membranes, or of glands, the brain, etc., 
such a defect gives rise to a cicatricial depression, ^^'umerous cicatricial 
defects in an organ may occasion an atrophy of the same characterized 
by an irregular configuration of the surface. 

The loss of the tissues en masse of larger portions of the body, as, for 
example, a toe or a toe-joint, is in man never again replaced. Such de- 
fects are only closed in by scar-tissue which on the superficial parts of 
the body becomes covered with surface epithelium. 

The regenerative capacity of tissues is in man and the mammals slight on the 
whole. This is dependent upon the fact that the individual tissues show a very high 
degree of differentiation, and that also in the event of proliferation they do not lose this 
diiferentiation to such an extent as to revert to so embrj^onal a state that, like the cells 
of the embryonal anlage, they are able to produce different forms of tissue. In spite 
of this limitation the regenerative powers of the tissues in general are sufficient to 
jestore the continuity of the tissues and to preserve intact the external covering of the 

J 



Fig. 135.— Peripheral zone of an embolic scar (Miiller's fluid, htematoxylin and eosin). a. Scar show- 
ing obliterated glomeruli, but no tubules ; ?), indurated tissue with atrophic tubules, the glomeruli being 
preserved ; c, normal cortical tissue ; d, island of normal tubules in the scar. X 30. 



body. If, as the result of a local loss of tissue, the life of the organism be endangered 
through the inability of the local tissues to restore the lost part, there exists in the 
case of many organs and tissues (liver, kidnej's) the power of compensating for such a 
loss through the growth of the remaining normal tissue. 

In the low^er animals the power of tissue-regeneration is much greater than in the 
case of the mammals; and further is much greater in the earlier stages of ontogenesis, 
so that, in many animals (tritons, ascidians, echinoderms, teleosts), the first two or even 
the first four segmentation cells still possess the power of forming an entire embryo. 
Insects possess during the larval state a very marked power of regeneration, which 
later is lost. 

In the case of protozoa each anim_al may quickly supplement itself through divi- 
sion. In the case of the fresh- water polypi small fragments of the body may develop 
again into the entire animal. The angle-worm is able to replace either its tail or head 
end when these a-re cut oft'. The wood-louse can replace its feet and antennae, the snail 



270 



THE PROGRESSIVE CHANGES. 



its tentacles and anterior extremit}', crabs and crayfish their claws and legs. Salaman- 
ders are able to restore their legs, eyes, and tails, and lizards and slow-worms their 
tails, when these are broken off. In the case of frogs, snakes, and fishes, on the other 
hand, the power of regeneration diminishes as the scale of animal life is ascended, yet 
this does not happen equally in the case of all animals, and animals closely related to 
each other may show very different capacities for regeneration. Further, in the same 
animal the regenerative power is not the same in all organs; for example, in tritons the 
regenerative caj)acity of the internal organs is slight. Moreover, the power to form a 
new portion of the body, as a tail or extremity, for example, does not prove that all 
the tissues of the portion of the body in question possess an especial capacity for pro- 
liferation. In crayfish and crabs the regeneration of the claws and legs takes place only 
from certain places; in injuries occurring to other points, the new extremit}^ is tlirown 
off only at that place, where a new-formation is possible. In tritons, fractures of the 
bones heal very slowly, although they are able to reproduce their extremities. 

Several years ago Graicitz advanced the view (" Ueber die schlummerden Zellen des 
Bindegewebes und ilir Verhalten bei progressiven Ernahrungstorungen," Yirch. Arch., 
127 Bd., 1892; "Atlas der pathologischen Gewebelehre," 1893) that cells may also arise 
from intercellular substance. He holds that, in the formation of connective tissue, cells 
are transformed into fibres and pass over into a non-nucleated resting -stage, in which 
condition thej^are invisible under the microscope. From these invisible slumbering -cells 
{ScTdumnier zellen) new cells may arise in inflammation and tissue-proliferation. In this 
theory of slumbering-cells, Grmcitz has brought forward as a new teaching, view's 
which were held years ago by Strieker and Heitzmann, and which had been regarded 
as buried ; but the w^ork done by him and his pupils in his institute contains nothing to 
substantiate this view. The well-known phenomena of proliferating and inflamed tis- 
siies have been described, but no observations have been published which can be re- 
garded as proving that cells may arise from intercellular substance — thatis, from invisi- 
ble slumbering-cells. 

§ 80. The cause of the cell=proliferation underlying all hyperplastic 
and regenerative new-formations of tissue varies according to the condi- 
tions under which the proliferation occurs. If the new tissue-growth 
leading to hypertrophy takes its origin from the anlage of the organism 
concerned or of a portion of the same, no new^ stimulus is necessary for 
its appearance; the attainment of the abnormal size is dependent only 
upon the condition that the new-formation of tissue does not lead to 
hindrances to growth before the full limit of development is reached. 
When the proliferation appears first at a later period, something addi- 
tional is necessary to cause an increase of the normal tissue -formation or 
to start again into activity the cell -proliferation which becomes quiescent 
at the close of the period of groAvth. 

In the case of both hyperplastic and regenerative proliferation the 
^' stimulus may consist simi)ly in the removal of hindrances to growth. 
Experience teaches that the majority of the cells of the body possess the 
power in a given case to divide, even those (connective -tissue cells, gland- 
cells, muscle-cells) in which the processes of cell-division wholly cease 
for long periods of time. This cessation of proliferation may be ex- 
plained by the assumption that the firm combination of the cells with 
each other and the formation of the intercellular cement inhibit further 
multiplication. It is also possible that chemical and unknown 
influences act in the same manner. Injuries and degenerations of the 
tissues of the most varied kinds can, through the loosening of the cells, 
and through phj^sical and chemical changes in the intercellular cement 
substance and of the tissue -fluids, cause such changes that all hindrances 
to the growth and division of cells are removed. 

In addition to the removal of hindrances to growth there may be 
present at the same time a formative stimulus, which increases both 
the reproductive capacity and the tendency toward reproduction. 
Further, such a stimulus may act independently — that is, without the 



REGENERATION AND REPAIR. 



271 



removal of the influences inhibiting growth — and this event is to be 
assumed in those cases in which after the loss of a portion of an organ 
the remaining portion (liver, kidney) undergoes a compensatory hyper- 
trophy. 

The stimuli which are able to excite growth and cell-division are 
known only in part. In those cases in which their action may be recog- 
nized they api^ear to be identical nyifh the stimuli which excite or increase 
functional and nutritive activity. In the case of the muscles hypertrophy 
is brought about by increased contraction following nervous excitation. 
Liver and kidney tissue undergo proliferation when, as the result of a 
loss of a large area of gland- tissue, the remaining portions are obliged to 
do an increased amount of work — that is, they must out of the circulating 
blood produce and secrete those substances which, if life is to be pre- 
served, must be given off either externally or within the body. 

Whether there exist still other formative stimuli cannot be said with 
certainty at the present time. An increased supply of nutrition, which has 
been believed by many to act as a formative stimulus, is not in itself 
sufficient to excite a new-formation of cells and tissue ; it gives rise only 
to an increased deposit of fat. The cells of the body are not fed, they 
feed themselves ; and an increase of nutrition depends uiDon the activity 
of the cells. An increase of the temperature of the tissues may hasten the 
process of cell-division and thereby further tissue-proliferation ; but it is 
doubtful if it can directly excite proliferation in a resting- tissue. The 
local action of heat, which has been observed to be followed by prolifer- 
ation (for example, in the skin), produces in the first place changes of a 
degenerative nature, so that the occurrence of proliferation may be also 
explained as due to the removal of influences inhibiting growth. 

Whether there are chemically active substances capable of exciting pro- 
liferation, besides those present normally in the body, cannot be decided 
at the present time. The fact that slight irritation of the skin (painting 
with iodine) can cause proliferation without preceding degenerative 
changes makes this appear probable. But it is more probable that, in 
spite of the negative findings, slight tissue- changes of a degenerative 
nature do occur, and that through these the inhibitory influences are 
weakened. 

Moreover, it must be noted that even the hypertrophy of muscles and 
glands following increased activity cannot be absolutely regarded as the 
direct result of a nervous or chemical stimulus, but rather must we 
assume that with the increased labor there is an excessive consumption of 
cell-elements ivhich excites regenerative processes, the latter leading not only 
to a restoration of the parts lost, but also to an increased building-up of 
the cell -mass and formation of new cells. 

Literature. 

(Eege7ieration. ) 

Aschoif: Regeneration u. Transplantation. Ergebn. d. allg. Path., v., 1900. 

Bard: La specificite cellulaire. Arch, de phys., vli.. 1886; Intern, med. Congr., 
Berlin, 1890; De Tinduction vitale ou influence specifique a distance des elements 
cellulaires les ims sur les autres. Arch, de med. exp., 1890; La specificite cellu- 
laire, Paris, 1899. 

Barfurth: Zur Regeneration dcx- Gewebe. Arch. f. mikr. Anat., 87 Bd., 1891; Regen- 
eration d. Keimblatter bei Amphibien. Anat. Hefte, Wiesbaden, 1893 ; Regenera- 
tion u. Involution. Ergebn. d. Anat., Wiesbaden, 189B-1900. 

Beneke: Die Ursachen der Thrombusorganisation, Beitr. v. Ziegler, vii., 1890. 



2T2 



THE PROGRESSIVE CHANGES. 



Bizzozero: Accroissement et regeneration dans I'organisme. Arch. ital. de biol, xxi., 
1894: Arch, per le Sc. 3Ied., xviii.. 1894; Influence de la temperature. Arch. ital. 
de biol., xxvi.. 1896. 

Caporaso: JSulla. ri-xeueraz. del midollo spinale della coda dei Tritoni. Beitr. v. Zieg- 
ler. v., 1889. 

Carnot: Les reiii'nerations d'orgaues. Paris, 1899. 

Carriere: Studien iiber die Regeneration der Wirbelthiere, Wlirzburg, 1880. 
Cattani: Ueber die Reaction der Gewebe auf specitische Reize. Beitr. v. Ziegler, vii., 
1890. 

Coen: Veranderungen d. Haut nach Einwirkung von Jodtinctur. Beitr. v. Ziegler, 
ii., 1887. 

Cohnheim : Yorlesungen liber allgemeine Pathologic, 1882. 

Colucci, F. : Intorno alia rigeuerazione degli arti e della coda nei Tritoni, Bologna, 1885. 
Delage : La structure du protoplasme, Paris, 1895. 
Deniarquay : De la regeneration des organes et des tissus, Paris, 1874. 
Fraisse: Die Regeneration von Geweben u. Organen bei Wirbelthieren, Berlin, 1885. 
Gotte: Ueber Eutwickelung u. Regen. des Gliedmaassenskelets der Molche, Leipzig, 
1879. 

Gruber, A. : Beitran'e zur Kenntniss der Phvsiolo2:ie und Biologic der Protozoen. 

Berichte der XaturL Ges. zu Freiburg i. B.\ 188Q; Biol. Cbl, iv., 1886. 
Harrison: Regeneration of the Tail of the Frog Larva. Bull, of Johns Hopkins 

Hosp.., X., 1899. 

Haeckel: L'rsprung und Entwickelung der thierischen Gewebe, Jena, 1884. 
Hansemann : Studien tlber die Specificitat, den Altruismus und die Anaplasie der 

Zellen, Berlin, 1893; Ueber die Speciticitat der Zelltheilung. Arch. f. mikr. Anat., 

43 Bd. , 1894. 
Herbst: Formative Reize. Biol. Cbl., xv., 1895. 
Klaatsch.: Stand der Keimblattfrage. Miincli. med. Woch., 1899. 
Kolliker: Die embrvonalen Keimblatter und die Gewebe. Zeitschr. f. wiss. Zool., 40 

Bd., 1884; 42 Bd., 1885. 
Marchand: Bez. d. path. Anat. z. Entwickeluugsgesch. Verh. d. Deut. path. Ges., 

ii., 1900. 

Martinotti: L^eber Hvperplasie u. Regeneration der drlisigen Organe in Beziehung 

auf ihre Functionsfahigkeit. Cbl. f. allg. Path., i., 1890. 
Merkel: Bemerkungen libT d. Gewebe beim Altern. Verh. d. X. intern, med. Congr., 

Berlin, 1891. 

Minot: Vererbung ii. Verjiingung. Biol. Cbl., xv., 1895. 

Morgan: Earthworm Regenerating a Tail in Place of a Head. An. Anz., xv., 1899. 

Morpurgo: Sur les rapports de la regeneration cellulaire avec paralysre vaso-motrice. 
Arch. ital. de biol., xiii., 1890; Sulla neoproduzione degli elementi cellulari dl 
auimali nutriti dopo un lungo digiuno. Arch, per leSc. Med., xiv., 1890; Ueber 
den phvsiol. Zellneubildunesprocess wahrend der Inanition. Beitr. v. Ziegler. iv., 
1889. 

Pekelharing: Ueber Endothelwucherung in Arterien. Beitr. v. Ziegler, viii.. 1890. 
Penzo: Influenza della temperatura nella rigenerazione. Arch, perle Sc. Med., xvi., 
1892. 

Podwyssozki, Jun. : Reijeneration der Drlisengewebe. Beitr. v. Ziegler, i., ii., 
1886-87. 

Rand: Reo-euerat. and Regulat. in Hvdra viridis. Arch. f. Entwlckelungsmech., viii., 
ix., 1899. 

V. Recklinghausen: Allg. Path. d. Kreislaufs u. d. Ernahrung, 1883; L'eber Akro- 

megalie. Virch. Arch., 119 Bd., 1890. 
Ribbert: Das patholog. "Wachsthum d. Gewebe, Bonn, 1896; Umbildungen. Virch. 

Arch., 157 Bd., 1899. 

Roemer: Ueber den formativeu Reiz der Proteine Buchner's. Berl. klin. Woch., 1891 ; 
Chem. Reizbarkeit thier. Zellen. Virch. Arch., 128 Bd., 1892. 

Roux, W. : Der Kampf der Theile im Organismus. Leipzig, 1881 ; Ueber die Specifi- 
cation der Furchungszellen und iiber die bei der Postgeneration und Regeneration 
anzunehmenden Vorgauge. Biol. Cbl., xiii., 1893. 

Samuel: Die Regeneration. Virch. Arch., 50 Bd.: Die histogeuetische Energie und 
die Symmetric des Gewebswachsthums, ib., 101 Bd; Das Gewebswachsthum bei 
Storiin2:en d. Circulation, ib., 108 Bd. ; Gewebswachsthum bei Storung d. Inner- 
vation,^ib., 113 Bd. 

Sokoloff: Bedingungen d. Bindegewebsneubildung in doppelt unterbund. Gefassen, 

Beitr. v. Ziegler, xiv., 1893. 
Strasser: Zur Kenntniss der functionellen An passung der quergestr. Muskeln, Stuttg., 

1883. 



KARYOKINESIS. 



273 



Thoma: Ueber Gefiiss- und Bindegewebsneubildmig in der Arterienwand. Yirch. 

Arch., 93, 95, 102, 105, and 112 Bd. ; Beitr. v. Ziegler, xi., 1891. 
V. Wag-ner: Ueber d. Verhaltniss d. Ontogenese zur Regeneration. Biol. Cbl., xiii., 

1898. 

Weig-ert: Die Vircliow'sclie Entziindungstheorie. Fortsclir. d. Med., vii., 1889; Zur 
patliol. Histol. des Neurogliafasergewebes. Cbl. f. allg. Path., i., 1890; Neue 
Fragestellungen. Deut. med. Woch., 1896. 

"Weismann: Das Keimplasma, 1892; Aeussere Einfliisse als Entwickelungsreize, Jena, 
1894 ; Thatsaclien u. Auslegimgeu in Bez. auf Regeneration. Anat. Anz., xv. , 1899, 

Welch: Adaptation in Pathol. Processes. Am. Journ. of 3Ied. Sc., 1897. 

WolfF: Das Gesetz der Transformation der Knochen, Berlin, 1892. 

Ziegler: Die neuesten Arbeiten liber Vererbung u. Abstammungslelire. Beitr., iv.,. 
1888; Die Ursachen der pathol. Gewebsneubildungen. Intern. Beitr., Festschr. f. 
Vircliow, Berlin, 1891 ; Die Reparation der Gewebe nach Yerletzungen. Deut. 
med. Woch., 1900. 
See also §§ 81-88. 

§ 81. The division of the nucleus and cen=body, upon which process 
the formation of new tissue depends, may occur in the first place through 
holoschisis (Flemming), or direct segmentation (Arnold) — that is, 
through a transverse constriction of the elongated nucleus and proto- 
plasm without an increase or characteristic grouping or movement of the 
chromatin elements of the nucleus. It appears, however, that the direct 
division of the nucleus leads to a new -formation of tissue — that is, to the 
production of cells which are able to form new tissue — only when it is 
connected with that form of cell -division known as karyokinesis or 




Fig. 136. Flu. 187. , Fl(i. 138. 



Fig. 136.— Enlarged nucleus. Increase in tbe cbromatin framework. 

Fig. 137.— Thick, open skein, witb segmentation of the threads into chromosomes ; the nucleolus and 
nuclear membrane have disappeared. 

Fig. 138.— Grouping of the completed chromosomes into a star- or wreath-form. 

karyomitosis (Flemming) or as indirect segmentation (Arnold), which 
is characterized by an increase of the nuclein or chromatin (Flemming), 
and a definite cycle of changes of form and movements on the part of the latter. 

Usually karyomitosis follows a typical course, as in the normal growth 
of tissue, but deviations from this are not infrequently seen in pathologi- 
cal new -formations. 

A resting necleus consists of an outer covering, the nnclear membrane, 
and the nuclear contents. The latter is composed of a colorless nuclear 
fiuid and the nuclear substance. To the nuclear substance belong the nu- 
cleolus and scattered granules and threads which often form a framework 
staining with nuclear stains. 

When the nucleus undergoes division, there usually occurs in the 
first place, an increase of the chromatin, and the chromatin framework 
becomes more distinct (Fig., 136). The nuclear substance then forms a 



274: 



THE PROGRESSIVE CHANGES. 



close sl'rhi, which with the disappearance of the nuclear membrane and 
the nucleolus becomes changed into an ope^i skein with thick threads (Fig. 
137), whose individual components divide themselves into nuclear seg- 
ments (Hertwig) or chromosomes (Waldeyer) (Figs. 137, 138). 

Tliese segments then grouj) themselves in the equatorial plane of the 
nucleus with their angles directed toward the centre, forming, when 




FIG. 143. FIG. 143. FlG. 144. 



Fig. 139.— Completely developed mother-star ; polar view. 
Fig. 140. —Mother-star ; equatorial \iew. 

Fig. 141.— Stage of metakinesis. Single loops visible, their angles pointed toward the pole ; delicate 
spindle-flgure within the nucleus. 

Fig. 143.— Daughter-star ; side view (nucleus barrel-shaped); spindle-figure in the nucleus and the 
radial arrangement of protoplasm are visible. 

Fig. 143. — Daughter-stars separated ; the upper one presenting polar aspect, the lower one a side view. 

Fig. 144.— Daughter-skein with fine threads (above), and with lattice-work (below). Completed di- 
vision of the protoplasm. 

viewed from the polar aspect, a wreath-like figure (Fig. 138), and later 
a star-like figure, lying in the equatorial plane, which has been desig- 
nated the mother-star (Figs. 139, 140), or the equatorial plate (Flem- 
ming). 

Sooner or later two poles become visible in the interior of the cell — 
that is, two extremely small spherules, which are known as the polm^ or 
central corjmscles or the centrosomes. At first these lie closely together, 
but later separate from each other and act as centres about which the 
nuclear elements group themselves. Between these there is formed the 
nuclear spindle (Figs. 141, 142) which consists of fine threads which do 
not stain with nuclear stains, and converge in the polar corpuscles. In 



KARYOKINESIS. 



275 



the neighborhood of the polar corpuscles themselves the granules of the 
protoplasm present a radial arrangement, giving rise to figures (Fig. 
142) which are known as ray -figures^ stars, or attraction- spheres. In the 
following stage of division of the nucleus, which has been designated 
metakinesis, a movement takes place among the chromosomes leading to 
the formation of unequal-sided loops, whose angles are directed toward 
the pole. Later the loops, following the direction of the spindle-fibres, 
move toward the poles and form two stars (Figs. 142, 143) which are 
known as daughter -stars. From the star-figures the daughter-star passes 
successively through the thick-skein and then the fine-skein stage (Fig. 
144, upper part) which finally changes into the nuclear /?-«meit'orA: (Fig. 
144, lower part). During the later stages of the process of division a 
new nuclear membrane is formed. 

The division of the celi=protoplasm usually takes place at the time 
the daughter -star changes into the ordinary nuclear condition, and con- 
sists in a constriction and separation of the protoplasm (Fig. 144). The 
radiating figures (Fig. 142) about the centrosomes are to be regarded as 
evidences of movements within the protoplasm. It is probable that a 
complicated interrelationship exists between the nucleus and cell-proto- 
plasm ; but the nucleus is to be regarded as the more highly organized sub- 
stance, as the centre of cellular potentiality. The nuclei are also the bearers 
of heredity, while the protoplasm governs the relations of the cell with 
the outer world. 

Variations from the typical l^aryokinesis may consist in the first 
place in the occurrence of a pluripolar division in place of the bipolar, so 
that two to six or more nuclear spindles and a correspondingly increased 
number of equatorial plates (Fig. 145, a) may be formed. Further, in 
place of the simple mother-star there may be formed a complicated figure 
out of the chromatin loops, from which 
several daughter- stars may be evolved, 
^^ot infrequently there occur asymmetrical 
divisions of the nucleus (Fig. 145, b, c), par- 
ticularly in tumors, but occasionally also 
in regenerative or inflammatory new-for- 
mations of tissue. 

There also not infrequently occur 
divisions of the nucleus which are char- 
acterized by abnormal size, abnormal rich- 
ness in chromatin, and manifold variations 
of form. As types of such division are 
the large oval or bean-shaped (Fig. 146), 
knobbed or convoluted, lobulated and 
branched (Fig. 147). wreath -shaped, 

linked, basket-shaped (Fig. 148), and otherwise -shaped nuclei. Finally, 
there are occasionally lo md in the cells more or less extensive, indis- 
tinctly-outlined heaps of granular and lumpy chromatin (Fig. 149). 

Such nuclear forms, with the exception of the polynuclear leucocytes, 
are found particularly in the cells of the bone-marrow, spleen, and 
lymph-glands, and also in tumors which arise from the bone-marrow or 
periosteum, but have been also observed elsewhere, particularly in sar- 
comata. Certain of these forms are appearances due to contraction, and 
have nothing to do with cell-division. In other cases these changes of 
size and form precede a division of the nucleus through constriction of 
certain portions, this process occurring sometimes with, sometimes with- 
16 




Fig. 145. — a, Pluripolar divislon-flgure ; 
b, c, asymmetrical divislon-flgures. 



276 



THE PROGRESSIVE CHANGES. 



out an increase of the chromatin- substance. Arnold has desigi:«n.t«ed the 
division by constriction with increase of the chromatin as indirect frag- 
mentation, that without such increase as direct fragmentation. Indirect 
fragmentation differs from mitosis or indirect segmentation in the lack 




FIG. U6. 




FIG. 147 



j 



Fig. 148. 




Fig. 149. 



Fig. 146.— Cell with oval, slightly knobbed giant-nucleus, rich in chromatin. 

Fig. 147.— Cell with lobulated giant-nucleus. Fig. 148.— Cell with basket-shaped giant-nucleus. 

Fig. 149.— Cell with large masses of chromatin. All these cells from a sarcoma of bone. (Stroehe^ 
Beitrage von Zitglc7\ VII.) 



of an orderly arrangement of the chromatin in threads and in the irregu- 
larity with which the separation of portions of the chromatin results in 
new nuclei. 

Variations in the division of the cell=protoplasm occur most fre- 
quenth^ either in a total failure of the i^rotoplasm to divide after the divi- 
sion of the nucleus has taken place, or in the delayed division after that 
of the nucleus; These phenomena are observed in both mitotic and ami- 
totic division of the nucleus, and lead to the formation of hinuclear cells. 
Through progressive nuclear division into two nuclei or through multiple 
division, there may be formed multinuclear giant=cells, which either 

persist as such or 
later undergo further 
division. 

The cause of the 
formation of giant - 
cells may lie in the 
especial varietv of 
cell. Cells of the 
spleen and bone -mar- 
row and of tumors 
arising from the bones 
show this phenom- 
enon with especial 
frequency. Prolifer- 
ating fat -cells like- 
wise often form mul- 
tinuclear giant -eel Is 
(Fig.l50,rt)- Further, 
this phenomenon is 
often seen when pro- 
liferating cells lie upon the surface of some foreign body. In the 
cellular new-formations caused by the tubercle-bacillus the formation of 
multinuclear giant-cells is a typical phenomenon. The adhesion of the 




Fig. 150.— Proliferating adipose tissue from the subcutaneous pannic- 
ulus, twenty-six days after cauterization with trichloracetic acid (forma- 
lin, haematoxylin). a, Multinuclear fat-cells; Ij, proliferating connec- 
tive tissue. X 300. 



KARYOKINESIS. 



277 



cellular protoplasm to a firm body, the enclosure by the cell-protoplasm 
of large foreign bodies (also fat-drops), and also the partial degener- 
ation of the protoplasm caused by bacteria, may be the factors hindering 
the division of the cell. 

Occasionally the protoplasm of the cell, during division, forms also 
buds or offshoots, and this phenomenon may occur either before or 
after the division of the nucleus. Into the buds or offshoots nuclei may 
later migrate (see new-formation of blood-vessels). 

According to RaU, whose studies were carried out on the large nucleated cells of 
cold-blooded animals, the closely wound mother-skein consists of several pieces, all of 
which are bent back to one end of the nucleus (called the polar field) (Fig. 151, a), 
leaving the pole itself free, while at the opposite end (the opposite polar field) {b) they 
extend across the pole. The transition from the close to the open skein (Fig. 152) is 
brought about by the threads becoming thicker and shorter, at the same time these 
divide so that the number of loops becomes increased. 

The stage of the segmented skein (Fig. 153), which follows next, is ciiaracterized 
especially by the longitudinal fission of the srjxirate loops, whereby the chromatin-sub- 




FKx. J5L Flu. L.5. Fig. 156. 



Fig. 151.— Close skein ; lateral aspect. Fig. 153.— Open skein ; lateral aspect. 

Fig. 153.— Final stage of the skein, with splitting of the threads. 

Fig. 154.— Mother-star. Fig. 155.— Metaklnesis. 

Fig. 156.— Daughter-stars. 

stance becomes divided into two equal parts. The further course of the karyokinesis 
is essentially directed toward the uniting of each half of chromatin threads into a new 
group. 

During the stage of the coarse open skein there has already begun to develop in the 
neighborhood of the polar Qeld a, spindle-shaped figui^e (Fig. 152, c), consisting of deli- 
cate threads which terminate in small shining bodies, the centrosomes. Later, this 
spindle wanders into the nuclear substance (Fig. 153), and exerts a directing influence 
upon the chromatin threads. In the plane of its equator the division of tlie nucleus 
later takes place. 

In order to initiate the process of division the loops of threads group themselves 
about the equator of the spindle in such a way that their angles point toward the centre 



278 



THE PROGRESSIVE CHANGES. 



of the spindle, tlms completing tlie mother-star (Fig. 154). At the same time the 
nuclear membrane disappears while from the poles of the spindle radially-arranged 
tibrils (Figs. 154-156) stream out into the cell-protoplasm (cytaster, attnirtion-splie re). 

M( t>'kni(.y/s is characterized by a separation of the daughter-tlu-eads arising from 
the longitudinal fission, which up to this time have remained parallel with each other; 
and it is completed sometimes by the threads of each pair (Fig. 155) moving toward 
the opposite poles. The new loops arising in this wa}^ have their angles directed tow- 
ard the poles. 

The daughter-stars (Fig. 156) are formed by the chromatin loops that have moved 
toward the poles of the spindle. 

The daughter-skeins (dispirem of Flemming) arising from the daughter-stars consist 
of loops of fibrils which are bent back at the point where the poles of the spindle are 
situated (Fig. 157, a) and leave one polar field {c, d) free from loops. 

The transition from the skein into the framework of the resting-nucleus (Fig. 157, 
h) follows {Rahl) the division of the cell-protoplasm, and is initiated by the chromatic 
fibres sending out processes. According to Flemming, Strassbiirger, and Retzius, the 
chromatin threads unite directly with one another. 

The significance of the nuclear corpuscles (nucleoli) is still a matter of dispute. 
FUmndng and Pfitzner believe that they are different from the nuclear framework, 
while others regard them as much-thickened nodal points of the fibrils of the frame- 
work. In what Avay they are again formed after the division of the nucleus is not 
known. 

The mv dear framework forms at its periphery a thick, basket-like layer, on the 
outer side of which lies another membrane, which does not stain. 

The spindle-figure, whose fibres stain but slightly with nuclear stains, is derived, 
according xo Fhinming -And Htrtirig. from the above-mentioned achromatic substance 

of the nuclear framework, while Strassburger believes 
that it arises from the cell-protoplasm. 

The ctutrosomes or polar corpuscles, which are always 
present in nuclear segmentation, are found also in rest- 
ing-nuclei ; but up to the present time they have been 
demonstrated only in a part of the cells, nio.st frequenth' 
in lymphocytes and the giant-cells of the bone-marrow. 
At the same time the investigations of von Kdlliker, 
Flrni ruing. J/. Ileidenhain, and others make it probable 
that the centrosomes are present in all cells, lying some- 
times in the nucleus, sometimes in the protoplasm, where 
on account of their small size the}' can be demonstrated 
only with difficulty. (The centrosomes do not stain with 
the ordinary nuclear stains, but with acid aniline dyes, as 
acid fuchsin and safranin.) Whether they are elements 
of the protoplasm or of the nucleus has not yet been de- 
cided. According to mn Beneden, Boveri, and Rabl, the 
mitosis of the nuclear substance is to be referred to a 
Fig. 157. — Daughter-skein (a), direct drawing-apart, starting from the divided centro- 
aBd dauRhter lauice-work (?)) : c, somes and brought about by the as^ency of the achro 
rinmf-^y'''oiar^lr™"^ According to J/. Eeidenhain, the central 

spin e , , pu ■ r . corpuscles are sharply circumscribed granules whicli 

possesss the power of assimilation, of growth and of 
multiplication by budding, whereb}' thej' are accustomed to form groups. Either alone 
or united in groups, they can form the central point of insertion of a system of con- 
tractile fil^res (spindle-figures, microsome rays), and consist of a specific substance (in 
a chemical sense) which is not present elsewhere in the cell. 

Fh iirnring designates the cell as a circumscribed mass of living matter, and distin- 
guishes in the cd<-h<'dy two different elements, one of which, the protoplasm {filarmass, 
hiitnint. jraii(Cirork) is somewhat more highly refractive and is arranged in the form of 
threads, while the other, tliQ parapjlasm {irderfilar mass, p^n-nrr itome) fills in the remain- 
ing space. The products of metabolism, granules, vacunles, and other inclusions, 
which the cells at times contain do not belong to the cell-substance. Arnold advances 
the view that many threads contain granules {microsomes, plasmosomes) or break up into 
rows of granules which are united by connecting links. The plasmosomes may also 
become changed into granules (see § 66). 




CELLS AND CELL-DIV^ISION. 



2Y9 



Literature. 

(^Cells and Cell- division.) 

Arnold: Kerne u. Kei-ntheiliingen in den Zellen des Knochenmarkes. Vii'ch. Arch., 
93 Bd., 1883; Ueber Kern- iind Zelltbeiluugen bei acuter Hyperplasie der Lymph- 
driisen und der Milz. lb., 95 Bd., 1884; Tbeilima:svorgange an den Knocbenmark- 
zellen. lb. , 97 Bd. , 1884 ; Ueber Kerntheilun g luid vielkernige Zellen. lb. , 98 Bd. , 
1884; Tbeilungsvorgange an den Wanderzellen. Arcb. f. mikr. Anat., xxx., 1887; 
Kern- u. Zelltbeiliingen in der Milz. lb., xxxi., 1888; Structur und Arcbitektur der 
Zellen. lb., lii., 1898; Flemming nnd die Mitosenlebre. Anat. Anz., xvi., 1899. 

Bardeleben: Karyokinese. Eulenburg's encj^klop. Jabrb., i., 1891. 

Bizzozero: Ueb. die Regeneration. Cbl. f. d. med. Wiss., 1886 (Lit.). 

Boveri: Zellenstudien I-II, 1887-88. 

Cornil: Multiplication des cellulues de la moelle des os. Arcb. de phj's., x., 1888. 

Demarbaix: Division et degenerescence des cellules geantes. La Cellule, v., 1889. 

Denys: La cytodierese des cellules geantes et des petites cellules incolores de la moelle 
des OS. La Cellule, 1886; Division des cellules geantes de la moelle des os d'apres 
les travaux de Arnold, Werner, Lowit et Cornil. Anat. Anz., iii., 1888; La Cellule, 
v.. 1889. 

Eberth.: Vircb. Arcb., 67 Bd. ; Kern- und Zelltbeilung wabrend der Entziindung u. 

Regeneration. Internat. Beitr., Festscbr. f. Yircbow, ii., Berlin, 1891. 
Fischer: Fixirung, Farbung und Bau des Protoplasmas, Jena, 1899. 
Flemming', W. : Kerntlieilung. Arcb. f. mikr. Anat., xvi., 1879; xviii.. 1880; xx., 

1882; xxiv., 1884; Vircb. Arch., 77 Bd. ; Zellsubstanz, Kern- und Zelltbeilung, 

Leipzig, 1882; Ueber Zelltbeilung. Verb. d. Anat. Gesellscb., Miiucben, 1891; 

Beitrage zur Kenntniss der Zelle. Arcb. f. mikr. Anat., xxix., 1887; Tbeilung u. 

Kernformen bei Leukocyten. lb., xxxvii., 1891 ; Amitotische Tbeilung im Blasen- 

epithel des Salamanders. lb., xxxiv., 1890. 
Frenzel: Zur Bedeutung der amitotiscben Kerntlieilung. Biol. Cbl., xi., 1891. 
Fuerst: Veriind. d. Epitb. durcb. Wiirme u. Kiilte (Riesenzellen durcli directe Kern- 

theilung). Beitr. v. Ziegler, xxiv., 1898. 
Galeoti: Chromatin in den Epithelzellen der Carciuome. Beitr. v. Ziegler, xiv., 1893; 

Erzeugung von Unregelmassigkeiten d. karyokinet. Processe. lb., 1893; xx., 1896. 
Gruber, A.: Biologic der Infusorien. Ber. d. Naturf. Gesellscb. zu Freiburg, 1886; 

Einflusslosigkeit des Kerns auf Bewegung, Erniihrung u. Wachstlium einzelliger 

Thiere. Biol. Cbl., iii., 1883; Zeitscbr. f. wiss. Zool., xxxviii., 1883. 
Hansemann : Ueber asymmetrisclie Zelltbeilung in Epithelkrebsen u. deren biologi- 

sche Bedeutung. Vircb. Arch., 119 Bd., 1890; Ueber pathol. Mitosen. lb., 123 

Bd., 1891; Stud. lib. d. Specilitat, d. Altruismus u. d. Anaplasie der Zellen, 

Berlin, 1893. 

Hertwig, O.: Bildung, Befruchtung u. Tbeilung d. thier. Eies. Morph. Jabrb., i., 
1875; iii., 1877; iv., 1878; Ei- u. Samenbildung bei Nematoden. Arch. f. mikr. 
Anat., xxxvi., 1890; Die Zelle und die Gewebe, Jena, 1893. 

Hess : Ueber Vermehrungs- u. Zerfallsvorgange an den grossen Zellen in der acut 
hyperplastischen Milz der Maus. Beitr. v. Ziegler, viii., 1890. 

Klebs, Or. : Ueber den Einfluss des Kerns in der Zelle. Biol. Cbl., vii., 1887. 

Kolliker: Zeitscbr. f. wiss. Zool., xlii., 1885. 

Kra£ft: Histogenese des Callus. Beitr. v. Ziegler, i., Jena, 1886. 

Krompecher: Die Melirtheilung. Cbl. f. allg. Path., v., 1894; Die mehrfache Kern- 
tlieilung, Wiesbaden, 1895; Mitosen mehrkerniger Zellen. Vircb. Arch., 142 Bd., 
1895. 

Lowit: Neubildung u. Zerfall weisser Blutkorperchen. Sitzber. d. K. Akad. d. Wiss. 
in Wien, 92 Bd., 1885; Neubilduug u. BeschatJenheit d. weissen Blutkorperchen. 
Beitr. v. Ziegler, x., 1891; Amitotische Kerntheilung. Biol. Cbl., xi., 1891; Cbl. 
f. allg. Path., i., 1890. 

Meves: Ueber eine Art der Entstehung ringformiger Kerne, Kiel, 1893. 

Nauwerck u. Steudel: Regeneration d. quergestreiften Musculatur. Beitr. v. Zieg- 
ler, ii., 1888. 

Nedjelsky : Amitotische Theil. in path. Neubild. Beitr. v. Ziegler, xxvii., 1900. 
Pfeffer: Bedeutung der ximitose. Ber. d. K. Sachs, Ges. d. Wiss. z. Leipzig, 1899. 
Pfitzner: Arch. f. mikr. Anat., xxii., 1883; Morph. Jabrb., xi., 1885. 
Podwyssozky: Regeneration d. Driisengewebe. Beitr. v. Ziegler, 1., ii., 1886-88. 
Rabl: Ueber Zelltbeilung. Morph. Jabrb., x., 1885; Anat. Anz., 1888, 1889. 



280 



THE PROGRESSIVE CHANGES. 



Reinke : Untersucliungen liber das Veihiiltniss der von Arnold beschriebenen Kern- 

formen zur Mitose und Amitose. Inang.-Diss., Kiel, 1891. 
Retzius, G. : Studien liber die Zelltlieilung, Stockholm, 1881. 
Roux, W. : Ueber die Bedeutung der Kerntlieilungsfiguren, 1883. 
Schlatter: Stand der Zellenlelire. Biol. Cbl., xix., 1889. 

Schottlander : Ueber Kerntlieilungsvorgange in dem Endotliel der artificiell entziin- 

deten Hornliaut. Arch. f. mikr. Anat., xxxi., 1888. 
Schwarz: Zur Theorie der Kerntheilung. Virch. Arch., 124 Bd., 1894. 
Strasburger: Zellbildung u. Zelltheilung, Jena, 1890; Ueber den Tlieilungsvorgang 

der Zellkerne u. d. Verhaltniss der Kerntheilung zur Zelltheilung. Arch. f. mikr. 

Anat., xxi., 1882; Die Controversen d. indirecten Kerntheilung. lb., xxiii., 1884; 

Das Protoplasma u. die Reizbarkeit, Jena, 1891. 
Stroebe: Kerntheilung u. Riesenzellenbildung in Geschwiilsten u. im Knochenmark. 

Beitr. v. Ziegler, vii., 1890; Cellulitre Vorgange u. Erscheinungen in Grcschwlilsten. 

lb., xi., 1891; Vorkommen und Bedeutung der asymmetrischen Karyokinesen. 

lb., xiv., 1893. 

Tang-l: Zellkorper u. Kern wahrend der mitotischen Theilung. Arch. f. mikr. Anat., 
xxx., 1887. 

Verworn: Die physiologische Bedeutung des Zelikerns. Pflilger's Arch., 51 Bd., 

1893. 

Waldeyer: Ueber Karyokinese. Deut. med. Woch., 188G, 1887. 
Weismann: Das Keimplasma, Jena, 1892. 

Wilson : The Cell in Development and Inheritance, New York, 1897. 

Zander: Ueber d. gegenwartigen Stand der Lehre v. d. Zelltheilung. Biol. Cbl., xii,, 

1892. 

Zieg-Ier, H. E.: Biologische Bedeutung der amitotischen Kerntheilung. Biol. Cbl., 
xi., 1891. 



(Attraction- spheres, Centrosomes, and Nuclear -spindle. ) 

vanBeneden: Rech. s. 1. fecondation. Bull, de I'Acad. Roy. Belgique, xiv., 1887. 
Boveri: Zellenstudien I.-II., 1887-88. 

Biirger: Was sind die Attractionsspharen und ihre Zellkorper? Anat. Anz., vii., 1892. 
Carnoy: Fecondation. La Cellule, xiv., 1898. 

Flemming": Ueb. Theilung u, Kernformen bei Leukocyten u. liber deren Attractions- 
spharen. Arch. f. mikr. Anat., 37 Bd., 1891; Attractionsspharen u. Centralkorper. 
Anat. Anz., 1891. 

!FoI:. Die Centrenquadrille. Anat. Anz., 1891. 

Hacker: Stand der Centrosomafrage. Verb. d. Deut. Zool. Gesellsch., 1894. 
Heidenhain, M. : Centralkorper. Arch, f . mikr. Anat. , 43 Bd. , 1894 ; Centralkorper 

u. Attractionsspharen. Anat. Anz., 1891; Kern- u. Protoplasma. Festschr. f. 

Kolliker, 1892. 

Hermann: Entstehung der karyokinetischeu Spindel. Arch. f. mikr. Anat., 37 Bd., 
1891. 

Hertwig- : Die Zelle und die Gewebe, Jena, 1893. 

V. Kolliker: Handb. d. Gewebelehre, i., Leipzig, 1889. 

Liustig- u. Galeotti: Cytolog. Studien liber pathol. Gewebe. Beitr. v. Ziegler, xiv., 
1893. 

Strasburger: Zu dem jetzigen Stand der Kern- u. Zelltheilungsfragen. Anat. Anz., 
1893. 



11. The Processes of Hyperplasia and Regeneration in the Various 

Tissues. 

§ 82. The morphological changes in the regeneration and hyperplasia 

of epithelium are relatively simijle. The karyoiiiitoses (Fig. 158, Or-d) 
show for the chief part a typical course. The division of the protoplasm 
takes place either in the later stages of the process of nuclear division 
or follows after the same. Occasionally processes are first formed from 
the proliferating epithelial cells, and into these nuclei later wander. 
Through separation from the mother -cell these processes may become 
independent cells. 



REGENERATION OF EPITHELIUM. 



281 




Epithelium arises only from epithelium, and, moreover, the different 
varieties of epithelium do not pass over into one another. It is to be 
noted, however, that under certain conditions — for example, in cases of 
inflammatory iiTitation of 
long standing — the regen- 
erating epithelium may 
change its character, so 
that pavement epithelium 
may occasionally be de- 
veloped in places which 
originally possessed strat- 
ified ciliated columnar 
epithelium. This may 
occur, for example, in the 
case of cicatrization of 
ulcers in the trachea. De- 
fects of ciliated columnar 
epithelium are in the first 
place repaired by low col- 
umnar or flat cells which 
later become changed into 
high columnar cells. 

Small losses of substance in the superficial epithelium are usually 
quickly replaced through regenerative growth of the neighboring cells 
(Fig. 159, d, d^, dj. In such cases it may be seen that the epithelium 
bordering upon the defect quickly pushes over the denuded surface and 
begins to proliferate. The division of the nucleus and cell-protoplasm 
takes place not only on the edge of the defect, but also at some distance 
from it. In the intestine the loss of the superficial epithelium is quickly 
made good by a proliferation of the ej)ithelial cells situated in the deep 
parts of the crypts of Lieberkiihn. Likewise glandular e4^)ithelium — 
for example, in the liver or kidneys — is quickly restored after loss, pro- 
vided the structure of the tissue — that is, of the basement membrane 



Fig. 158.— Regenerative proliferation of the epithelium of 
bile-ducts, in the neighborhood of a wound of the liver Ave days old 
(Flemming's solution, safranin). a. Enlarged nucleus of epi- 
thelial cell, with increase of chromatin ; b, epithelial cell with 
mother-skein ; c, epithelial cell with mother-star ; d, epithelial 
cell with daughter-skein ; /, connective-tissue cell with daughter- 
star. X 400. 




5 

' c 



Fig. 159.— Healing of blister caused by a burn (alcohol, alum-carmine). Section through the skin of a 
cat's paw, forty-eight hours after the production of a blister, a. Horny layer ; 5, rete Malpighii ; c, corium ; 

d, newly formed epithelium; di, d^, newly formed epithelium already differentiated into different layers; 

e, old, degenerated epithelium ; /, pus-cells ; g, exudate ; /(, sweat-glands. X ~5. 




upon which it rests — is not changed. After destruction of liver-tissue 
both liver-cells and the epithelium of the bile-ducts (Fig. 158) prolif- 
erate, and the cell-division attendant upon an injury to the liver may 



282 



THE PROGRESSIVE CHANGES. 



extend to a relatively great distance from the wonnd. Experimental 
wonnds of the liver heal through the formation of connective tissue, into 
which only offshoots of the bile-ducts penetrate, while a local reproduc- 
tion of liver-tissue does not take place. Likewise, in the kidneys, testi- 
cles, thyroid, and ovary the local production of glandular tissue in the 
connective-tissue scar is very slight or wholly wanting, and does not 
lead to the formation of functionating tissue. In the salivary and mu- 
cous glands, on the other hand, there occurs a branching of the gland- 
ducts, and a new-formation of glandular alveoli. 

When portions of the mucosa and submucosa of the intestine are lost 
as a result of ulcerative processes, there occurs during the process of 
healing a glandular proliferation, which, according to the nature of the 
defect, forms partly typical, partly atypical (Fig. 133, i) glands which 
grow into the submucosa. The new gland-formation takes its start from 
the old glands, whose epithelium pushes over the edge and base of the 
ulcer (Fig. 133, g, h) and also lines any depressions which may happen 
to be present (k). In a similar manner ulcerative defects of the stomach 
mucosa are again made good; and even extensive ulcers may become 
covered over with a gland-containing mucosa, although the glands do 
not for the most part show a typical development — ^that is, are not trans- 
formed into characteristic gastric glands. 

The epithelial portions of the uterine mucosa which are in part lost, 
as a physiological process, during menstruation and parturition, and are 
afterward replaced, may be restored in a similar manner in the healing 
of pathological defects of the endometrium. The new- formation of epi- 
thelium takes its origin from the glandular remains. 

Compensatory hypertrophy of a kidney or liver, as the result of the 
loss of kidney- or liver-tissue, is brought about through the formation of 
new gland-cells, and the enlargement of existing renal tubules, or liver-rods 
respectively. After extirpation of one kidney the beginnings of compen- 
satory hypertrophy are recognizable even on the third day, by the ap- 
pearance of division figures in the epithelium of the urinary tubules; 
and there then follows a further j^roliferation, continuing for some time, 
of the epithelium of the uriniferous tubules and glomeruli as well as of 
the cells of the vessel -walls, as a result of which all the parts become 
enlarged. In the liver the lobules are enlarged, but no new-formation 
of these occurs. 

Literature. 

(^New -formation of Ejyithelinm and Gland- Tissue.) 
Arnold: Epitlielreireneratioii. Yircb. Arch., 4(3 Bd., 1869. 

Babes et Manicardite: Prolifer. des cellules liepatiques. Ann. de VInst. de path, de 
Boucarest, \., 1895. 

Barbacci: Rigeneraz. fisiol. degli element! epiteliali. Arch, per le Sc. Med., xiil., 
1889. 

Beltzow: Regen. des Harnblasenepithels Yirch. Arch., 97 Bd., 1884. 

Bizzozero: Regen. d. Drilsenzellen. Yirch. Arch., 110 Bd. ; Arch, per le Sc. Med., 

xi., 1887; Die schlauchformigen Drlisen d. Magendarmkanals. Arch. f. mikr. 

Anat., 32 Bd., 1893. 
BockendaM: Regen. v. Flimmerepithel. Arch. f. mikr. Anat., xxiv., 1885. 
Bossi: Reprod. de la muqueuse de Tuterus. Arch. ital. de Biol., xxiv., 1895, 
Coen: Yeranderungen der Haut nach der Einwirkung von Jodtinctur. Beitr. v. Zieg- 

ler, ii. ; Zur Anatomic der Milchdriise. lb., ii., 1887. 
Coen e D'Ajutolo: Sulle alterazioni istologiclie dei reni, dei muscoli, dello stomaco, 

degli intestini e del fegato nel avvelenamento cronico di piombo. Beitr. v. Ziegler, 

iii., 1888. 



THE NEW-FORMATION OF BLOOD-VESSELS. 



283 



Cohnheim: Epitlielregeneration. Vircli. Arch., 61 Bd., 1874. 

Cornil et Carnot : Regen. cicatricielle des conduits muqueux. Arch, de med. exp.^ 
X., 1898; Keg. des cavites muqueuses. lb., xi., 1899; Cicatrisat. des plaies du f oie. 
Sem. med., 1898. 

Eberth: Epithelregeneration. Yirch. Arch., 67 Bd., 1876. 

Fuckel: Regen. d. Submaxillar- u. Infraorbitaldrlisen. Inaug. Diss., Freiburg, 
1896. 

Flemming": Regen. v. geschicht. Plattenepithel, Darmepithel u. Flimmerepithel des 
Eileiters, Follikelepithel des Ovarium. Arch. f. mikr. Anat., xviii., xxiii., xxiv., 
1880-85. 

Golg-i, C: Neoformazione dell' epitelio dei canalicoli oriniferi. Arch, per le Sc. Med., 

vi., 1881; Arch. ital. de Biol., ii., 1882. 
Grifidni: Contribut. alia patol. del tessuto epitel. cilindr., Torino, 1884; Arch. ital. 

de Biol., v., 1882; Sulla riproduzione parziale del testicolo. Arch, per le Sc. Med., 

xi., 1887 ; Sulla riproduzione degli organi gustatori. Rendiconti dell' Istituto Lom- 

bardo, 1887. 

Griffini u. Vassale: Ueber d. Reproduction d. Magenschleimhaut. Beitr. v. Ziegler, 
iii., 1888. 

Hochhaus: Gewebsveranderungeu nach Kalteeinwirkung. Yirch. Arch., 154 Bd., 
1898. 

Jatta: Rigen. dell' epitelio del rene. x\rch. per le Sc. Med., xxi., 1897. 

Jung": Reg. d. Uterusschleimhaut nach Verletzuug. Cbl. f. Gyn., 1897. 

Kahn: Etude sur la regeneration du foie, Paris, 1897. 

Karg": Studien liber transplantirte Haut. Arch, f, Anat. u. Phys., 1888. 

Loeb: Regeneration des epithels. Arch. f. Entwickelungmech., 1898; Ueber das 

Wachsthum des Epithels. Ibid., 1901. 
Mall: Healing of Intestinal Sutures. Johns Hopkins Hosp. Rep., i., 1887. 
Martinotti: Ueber Hyperplasie u. Regen. der driisigen Elemente in Bez. auf ihre 

Functionsfahigkeit. Cbl. f. allg. Path., i., 1890. 
Mayzel: Theilung der Kerne in Epithelzellen. Cbl. f. d. med. Wiss., 1875. 
V. Meister: Recreation des Lebergewebes. Beitr. v. Ziegler, xv., 1894. 
Morpurg-o: Zellneubildung wahrend der Inanition. Beitr. v. Ziegler, iv., 1889. 
Neese: Verhalten d. Epithels bei Heilung v. Wunden d. Hornhaut. v. Graefe's Arch., 

xxxiii., 1887. 

Petrone: Du proc. regen. sur le poumon, sur le foie et le rein. Arch. ital. de Biol., 

v. , 1882. 

Piccoli: Rigenerazione parziale della prostata. Arch, per le Sc. Med., xxiv., 1900. 
Pisenti: Sur la cicatrisation du rein, etc, lb., vi., 1884. 

Podwyssozky : Regen. der Driisengewebe. Beitr. v. Ziegler, i., ii., 1886-87. 
Pogg>i: La cicatrisation immediate des blessures de I'estomac. lb., iii., 1888. 
Ranvier: Mecanisme de la cicatrisation. Lab. d'histol. du College de France, 1900. 
Ribbert: Regeneration der Mammilla. Arch. f. mikr. Anat., 37 Bd., 1891. 
Sanfelice: Regeneration du testicule. Arch. ital. de Biol., ix., 1888. 
Schlatter: Traumat. Leberverletzungen. Beitr. v. Bruns., xv., 1896. 
Simanowsky : Reg. d. Epithels d. Stimmbandes. Arch. f. mikr. Anat., xxii. 
Stroebe: Acute Leberatrophie. Beitr. v. Ziegler, xxi., 1897. 

Tizzoni: La fisio-patologla dell' epitelio pavimentoso stratificato. Arch. ital. de Biol., 

vi. , 1884. 

Vossius: Regen. d. Epithels der Cornea, v. Graefe's Arch., xxvii., 1881. 
Wath.: Regeneration d. Uterusschleimhaut. Arch. f. Gyn., 49 Bd., 1895. 
Wolff: Die Nierenresection u. ihre Folgen, Berlin, 1890; ref. Virch. Arch., 161 Bd. 
v. Wyss: Epithelregeneration. Virch. Arch., 69 Bd., 1877. 

Ziegler: Ursachen d. pathol, Gewebsneubildungen. Intern. Beitr., Festschr. f. Vir- 
chow, ii., Berlin, 1891. 



§ 83. The new=formation of bIood=vessels plays a very important 
role in hyperplasia of the most varied tissues. If connective tissue, 
bone, or glandular tissue is to be reproduced in any considerable 
amount, the new-formation of blood-vessels is essential, since it is only 
through these that sufficient nutrition can be brought to the growing 
tissue. 

The development of new blood-vessels takes place through the forma= 
tion of offshoots from the sides of the walls of preexisting vessels (Fig. 
160). In the vessel-wall there occurs a proliferation of cells, particu= 



THE PROGRESSIVE CHANGES. 



larly of the endothelium (Fig. 161), in which the division of the 
nucleus occurs by karyomitosis. 

As the first step in the formation of a new vessel, there is seen on the 
outer side of some capillary loop a tent-like elevation which terminates 
in a fine protoplasmic thread (Fig. 160, a), standing out from the vessel, 
and gradually becoming longer and longer, while the granular mass like- 




FiG. 160.— Development of l)loocl- vessels by formation of offshoots ; from preparations taken from in- 
flammatory granulations, a, b, c, d. Different foruis of offshoots, some solid {b, c), others becoming hol- 
low (a, 7), (?). some simple [a. d), some branching (/;, c), some without nuclei (a, cl), some with nuclei 
{/>. c); (?, offshoot to wliich fibroblasts have applied themselves. 

wise grows out at the same time. There is thus formed at the beginning 
a solid granular arch of protoplasm, which ends in a protoplasmic thread {a), 
and after a certain time comes to contain nuclei. This thread may 
penetrate into another vessel, or may unite with some other arch which 
it meets, or finally may return to the same vessel from which it started. 

Further, from the solid arch itself new secondary arches may spring 
(Fig. 160, 1), c), or at its end there may be formed a club-shaped swell- 
ing {c). 

The originally solid arch becomes hollow after a certain time (&, a) 
through the liquefaction of its central part, and the space thus formed 
either immediately or very soon comes to communicate with the lumen 
of the blood-vessel {a), or else there is developed from within the vessel 
an extension of the vessel-lumen into the arch. The blood of the mother- 
vessel finds its way at once into the cavity of the daughter-vessel and 
widens it. As the hollowing-out process constantly advances and ex- 
tends to the point of entrance of the protoplasmic arch into another 
blood-vessel, there is finally formed a new cai)illary loop permeable for 
blood. 

Immediately after the opening of a way for the blood the capillary 
tube possesses a homogeneous wall. After a certain length of time the 
protoplasm groups itself about the nuclei, which have in the mean time 



THE NEW-FORMATION OF BLOOD-VESSELS. 



285 



divided and multiplied in tlie wall, so that ultimately tlie capillary 
comes to be made up of flattened endothelial cells. As Arnold has 
shown, the boundaries of the individual flattened endothelial cells may 
be made visible through the injection of a solution of silver into the ves- 
sel. At this time the wall for the greater part appears much thickened, 
partly from the proliferation of the cells of the vessel-wall, but also 
partly from the fact that formative cells from the neighborhood heap 
themselves u^^on the surface of the young vessel (Fig. 160, d), adapt 
themselves to the wall, and so strengthen it. 

At the time of the formation of the offshoots, the endothelial cells of 
the capillaries are swollen, so that they form cells rich in protoplasm, 
which often in proliferating tissues reach such a size that the cross-sec- 
tion of a capillary looks not unlike a gland-tube lined with epitheliuiu 
(Fig. 162, d). At the same time di\dsion-figures appear in the endo- 
thelium (Fig. 161, a-c), and later the division of the nucleus and cell- 
protoplasm takes place. 

Just in what relation this j^roliferation stands to the formation of the 
offshoots is not yet clearly understood ; but doubtless the latter spring 
from proliferating cells and represent cell-proc- 
esses of the same. The proliferation of endothe- 
lium, on the other hand, does not always lead to 
a new-formation of vessels, but may result only 
in a thickening of the vessel-wall and finally in 
an obliteration of the lumen. 

In the transformation of newly formed capil- 
laries into arteries and veins — a change which 
must always occur in the case of extensive new- 
growths — the increase of tissue is the result of the 
continued proliferation of the cells of the vessel- 
wall. The individual elements of the arteries 
and veins are then developed from this formative 
material through especial jirocesses of differentia- 
tion. 

Three varieties of new-formation of blood-vessels are de- 
scribed by different authors — the primary, secondary, and 
tertiaiy, the last of which is described above. 

In the primary form the cells of the germ-tissue are 
directly transformed into red blood-cells and the elements of 
the blood-vessel walls, in such a manner, that the germ-cells 
unite to form strands whose axial portion becomes changed 
to red blood-cells, while the peripheral parts become the 
vessel -wall. Such a form of vessel-development, which 
occurs in the area germinativa, does not take place patholo- 
gically. 

In the secondarj^ form, according to BillrofJ), 0. Weber, Eindfleiscli, and Cornil {I.e., 
§ 82), spindle-cells unite to form cords in such a way that a canal is formed between 
them. Whether such a mode of vessel-formation actually occurs, appears doubtful. 

It is probable that these observations are based upon errors due to the fact that 
spindle-cells very early arrange themselves upon the vessel-buds, cover them up, and 
form cords of cells about them. 

Literature. 

(JS'ew- formation of Blood-vessels.) 

Arnold: Die Entwicklung d. Blutcapillaren. Yirch. Arch., 53 Bd., 1871; 54 Bd., 
1872. 

Billroth.: Untersuch. liber die Entwickelung der Blutgefasse, Berlin, 1856. 

Coen: Verand. d. Haut nacii Einwirkung von Jodtinctur. Beitr. v. Ziegler, ii., 1887. 




Fig. 161.— Two vessels of the 
papillary body, whose endo- 
thelial cells are in process of 
proliferation (six days after 
painting' the back of the foot 
with tincture of iodine) (Flem- 
ming's solution, safranin, and 
picric acid), a. Nucleus with 
chromatin framework: 7), b,, 
skein-forms; c, mother-star; 
d, connective-tissue cell with 
nuclear division-figure ; e, 
mononuclear leucocytes. X 
350. 



286 



THE PROGRESSIVE CHANGES. 



Flemming: Theilung voii Pigmentzellen u. Capillarwandzellen. Arch. 1 mikr. Anat., 
35 Bd., 1890. 

Hertwig: Lelirbucli der Entwickeluugsgeschiclite, Jena, 1893. 

Kuborn: Developp. des vaisseaux daus le foie de I'embryon. Anat. Anz., v., 1890. 
Nothnagel: Die Entstehung des Collateialkreislaufs. Zeitscbr. f. kliii. Mtd., xv., 
1889. 

Ranvier: Traite technique d'histologie, 18T6. 

Thiersch: Haudb. d. Cbir. von v. Pitha ii. Billroth, i. ; Arch. f. kiln. Chir., xvii., 1874. 
Thoma: Ilistogenese imd Histomechanik des Gefasss3'stems, Stuttgart, 1893. 
Yamagiva: Entziindliche Gefassneubildung. Yirch. Arch., 132 Bd., 1893. 
Ziegler : Ueber pathologische Bindegewebs- uud Gefassneubildung, Wiirzburg, 1876. 

§ 84. The connect! ve=tissue structures are almost all capable of 
both hyperplastic and regenerative i^rolif eration. This is especially true 
of unformed and formed connective tissue, the periosteum and the bone- 
marrow; while cartilage possesses but a slight regenerative capacity, 
and fully developed bone none at all. Usually proliferating fibrous con- 
nective tissue gives rise to fibrous tissue, both in the case of independ- 
ent formations of connective tissue and in the supporting tissue of the 
glands, lungs, lymi^h-glands, and brain. The periosteum, bone-marrow, 

l^erichondrium and cartilage 
produce in addition to fibrous 
connective tissue and marrow- 
tissue also cartilage and bone. 

Hyperplastic and regener- 
ative proliferations of the con- 
nective tissues are ushered in by 
cell-division in the course of which 
the karyomitoses, described 
above (Figs. 158, /; 161, d; 
162, h, c), occur. 

After injuries of the tissue 
these i)roliferations begin very 
soon, as, for example, in wounds 
of the skin, or in fractures of 
the bones; in the latter case 
even as early as the second day 
single cells of the periosteum 
have become enlarged and show 
division-figures. Besides mitoses, direct division of the nuclei also takes 
pjlace. 

WTien only a few cells are destroyed in the event of an injury to the 
tissue newly formed cells replace those destroyed without the occurrence 
of any marked slructural changes in the tissues. If, on the other hand, 
under pathological conditions, a considerable amount of new tissue is 
produced within a short time, the proliferating cells form an embryonic 
tissue consisting essentially of cells and blood-vessels (Fig. 162). The 
extent of such formation naturally varies greatly and is dependent 
partly upon the capacity of the tissue for proliferation, and partly upon 
the lesion leading to the proliferation. Thus, for example, the perios- 
teum, proliferating after the fracture of a bone, forms a continuous 
layer of proliferating embryonic tissue (Fig. 162), while proliferating 
cartilage, on the other hand, produces only small foci of embryonic tis- 
sue consisting of a limited number of cells. 

Proliferating cells are always larger than the cells of fully developed 
and resting connective tissue which are relatively poor in protoplasm. 




Fig. 162.— Proliferating periosteum, four days after 
fracture of a bone (Flemming's solution, haematoxylln). 
o. Pale formative cells with large nuclei: 7), osteoblast 
with division-tls-ure : c. two cells shortly after division, 
showing thread-skein in nucleus ; (7, blood-vessel with 
proliferating endothelium ; e, endothelial cell with 
nuclear divisiou-hgure ; /, small, deeply staining for- 
mative cells ; (/, leucocytes. X 3.50. 



REGENERATION OF CONNECTIVE TISSUE. 



2S7 



They contain large, bladder- like nuclei with nucleoli, and for the greater 
part only one or two nuclei (Figs. 162, 163), though multinuclear cells 
(Fig. 163, c,) the so-called giant-cells, also occur. 

Since all these cells are the antecedents of the future tissue they are 
designated as formative cells, those giving rise to fibrous connective 




Fig. 163.— Isolated cells from a granulating wound (picrocarmlne). a, Mononuclear; ai, polynuclear 
leucocytes ; /), different forms of mononuclear formative cells ; c, formative cell with two nuclei; Ci, mul- 
tinuclear formative cells ; d, formative cell in stage of connective-tissue formation ; e, fully developed con- 
nective tissue. X "»(i<i. 



tissue are called fibroblasts (Figs. 168, h, c, d, e; 161, a), while those 
forming cartilage and bone are known as chondroblasts (Fig. 165, a, c) 
and osteoblasts (Fig. 162, a, b, c) respectively. 

The shape of the formative cells varies greatly (Fig. 163, b, c, d, e), 
and is dependent, partly upon intrinsic causes — that is upon spontaneous 
changes of form — partly upon the influence of the environment, which 
under certain conditions comx3els the cells to take certain definite forms. 
The cells producing connective tissue usually 
present the greatest variety of form. 

When connective tissue is developed 
from a cellular embryonic tissue, either Jine 
fibrillce (Fig. 163, d, e) appear at once in 
certain parts of the cell -protoplasm, or there 
is formed first a homogeneous intercellular sub- 
stance (Fig. 161, b) in which the fibrillfe 
later appear. The formative cells at the 
same time diminish in size, and come to 
lie, for the most part, in small clefts (Fig. 
163, e) in the ground-substance. 

Elastic fibres first appear in newly 
formed connective tissue at a late stage, and 
at the beginning form very fine fibrillse, which (Fig. 165, b) represent 
processes of older thicker fibrillse (a). It is difficult to trace their 
origin. Whether they arise from the cells, or represent a differentiation - 
product of the fibrillar intercellular substance is yet a matter of dispute. 



# ^ * 




Fig. 164.— Development of connec- 
tive tissue from fibroblasts (MuUer's 
fluid, picrocarmlne) . a. Fibroblasts : 
h, hyaline ground-substance with 
scattered flbrillae ; c, fibroblast with 
adjacent fibres. X 400. 



288 



THE PROGRESSIVE CHANGES. 



The connection of the newly formed fibres with older elastic fibres 
speaks rather for the latter hypothesis. 

They develop most abnndantly in newly formed connective tissue in 
the blood-vessels and in the skin, but such a new-formation of elastic 




Fig. 165.— Scar of the skin, two years old, showinir newly formed elastic fibres (alcohol, orcein), a, Ce- 
rium with normal elastic tibres ; Z), scar witli newly formed elastic fibres, x 500. 



fibres occurs also in other regions, as, for example, in connective-tissue 
proliferations inside of glands. 

In the development of hyaline cartilage there appears betAveen the 
cells a hyaline basement-substance (Fig. 166,/), while the chondroblasts 
(c) at the same time assume a more rounded form (d). In time the 
ground-substance increases, the chondroblasts grow smaller and come to 
lie in rounded cavities whose walls are denser than the rest of the ground- 



/I 




#1 



-4 



Fig. 166.— Periosteal formation of cartilage In a fracture five days old (Flemming's solution, htema- 
toxyhn. glycerin), o, CeHular embryonic tissue; h. caiTilaore; c\ proliferating periosteal formative cells ; 
i7. cartilage-cells; d■^, nuclear division-figures in cartilage-cells; e. ground-substance of embryonic 
tissue; f, ground-substance of the cartilage; g, capsule of cartilage-cells ; /i, proliferating endothelium of 
a blood-vessel. X 320. 

substance and later form the part of the basement -substance called the 
cartilage- capsule (g). 

In the development of bone from cellular embryonic tissue there 
appears between the formative cells a dense homogeneous or fibrillated 



NEW- FORMATION OF BONE. 



289 



basement -substance (Figs. 167, e, /; 168, c), which later on becomes im- 
pregnated with lime-salts. When the ground -substance between the 
osteoblasts is already of a loose fibrillar nature (Fig. 167, d) the transition 




Fig. 16T.— Myelogenous formation of bone from masses of osteoblasts (Miiller's fluid, picric acid, bcema- 
toxylin, carmine). Preparation from the inner callus of a fourteen-day old fracture of the fibula of a man 
twenty-five years of age. a, Fat-cells of the bone-marrow ; h. bone-marrow containing no fat; c, scattered 
osteoblasts; d, groups of osteoblasts; c, first step in the formation of the ground-substance of bone ; f, de- 
veloping trabeculae of bone ; g, layer of osteoblasts lying upon the newly formed trabeculie of bone ; 7i, 
blood-vessel. X 150. 

into bone -tissue is brought about through a thickening of the ground- 
substance {e, /). Through chemico-physical changes of its ground-sub- 
stance cartilage may become directly transformed into bone (see Metaj)lasia). 
The osteoblasts come to lie in irregular spaces furnished with processes 
(Figs. 168, c; 169, b), and are then usually known as bone-corpuscles. In 




Fig. 168.— -Formation of osteoid trabeculEe from the proliferating periosteum. Preparation from a 
fourteen-day old fracture (Miiller's fluid, picric acid, heematoxylin, carmine), a. Fibres belonging to the 
outer periosteum ; &, embryonic tissue ; c, osteoid tissue ; d, cartilage ; e, bone-marrow. X 75. 

extensive development of cellular embryonic tissue the change into bone 
is limited to certain parts of the tissue, so that within the embryonic 
tissue trabeculse (Fig. 168, c) are formed, which, so long as they do not 



290 



THE PROGRESSIVE CHA^'GES. 



undergo full development into bone and do not become calcified, are 
called osteoid trabeculae. The embryonic tissue (b) lying between be- 
comes clianged into marrow=tissue by the cells becoming united to each 
other through processes, while between them there apx^ears a fluid base- 
ment-substance, in which round-cells later appear embedded. If only a 
little bone-tissue is to be formed and deposited upon old bony trabeculae, 
the osteoblasts (Fig. 1G9, e) arrange themselves upon the surface of the 

latter, and these later on j^roduce bone 
(b) in the manner described above. 

Mucous tissue arises from embryonic 
tissue through the formation of a mucin- 
containing, homogeneous, gelatinous base- 
ment-substance between the cells which at 
least in part become united through proc- 
esses to form a network. 

Lymphadenoid tissue can develop 
from embryonic tissue through the for- 
mation of a supporting reticulum from a 
j)art of the cells, while lymphocytes gather 
in the meshes of this network, the spaces 
of which, contain lymph. In injured lymph-glands, the cells of the retic- 
ulum proliferate and form ordinary fibrous tissue; a reticular develop- 
ment of this connective tissue into lymphadenoid connective tissue either 
does not take place at all or but to a very slight degree. 

Spleen=tissue is not formed anew after injury to this organ; the 
wound heals through ordinary cicatrization. Comi)ensatory hypertrophy 
does not take place after the removal of large portions of the organ. 

Fat=tissue arises through the taking up of fat into the cells of em- 
bryonic tissue, mucous tissue or fibrous connective tissue, the cells be- 
coming changed into fat-cells through the confluence of the fat-droi)lets 
which they take 

The basement=substance of the tissues described above is a product 
of the protoplasm of the formative cells. Whether in its formation 
portions of the cell-protoplasm are directly changed into basement-sub- 
stance, or whether they secrete the latter, or separate it from the inter- 
cellular fluid, is often a difficult question to answer ; but it is probable 
that only the first two methods of formation occur. In suitable speci- 
mens it may often be seen that the fibrillce, both of the connective tissue 
and of osteoid tissue, as well as of newly-formed cartilage tissue are con- 
nected with cells — that is, they represent simple or branched processes of 
the same, or they may even enter into the granular protoplasmic sub- 
stance (Fig. 163, d), thus forming an integral part of the cell -body. In 
other cases such a conne<!tion cannot be demonstrated. 

With the further differentiation of the fibrillar basement -substance, 
the fibrillie, to a great extent, become separated from the protoplasm. 

Fibrillar connective tissve can develop from any of the connective tissue possessing 
the power of proliferation, but there must first be formed an intermediate stage of em- 
bryonic tissue. 

Bone arises chiefly from the periosteum, perichondrium, and bone-marrow : but 
may also develop from" other connective-tissue substances, as, for example, from the 
intermuscular connective tissue. 

Cartilcifie arises chiefly from proliferating perichondrium, periosteum, bone-mar- 
row, and cartilage itself ; but may also be developed from other connective tissues, as, 
for example, in connective tissue of the testicle and parotid. The cartilage cells near a 
lesion ma}^ under certain circumstances proliferate and form a large-celled embryonic 




FKt. ItjlJ.— Foruiation of bone. Through 
deposits made by osteoblasts upon the sur- 
face of old bone (Miilier's fluid, picric acid, 
haematoxylin, carmine), a. Old bone; /i, 
newly formed bone ; c, osteoblasts. X 200. 



NEW-FORMATION OF CONNECTIVE TISSUE. 



291 



tissue, but this does not reach nnj great size. In the proliferation of cartilage-cells 
within cartilage the cell-multiplication and new-formation of cartilage occur in the same 
way as in the physiological proliferation of this tissue. Very often the newly-formed 
cartilage is only a transitory tissue, and is soon transformed again into bone and mar- 
row-tissue, or into connective tissue. 

New lymphaclenoid tissue may, under pathological conditions, arise either from 
lymphadenoid tissue, or fat-tissue {Bayer) or from librillated connective tissue. It is 
formed from the latter most frequently in the connective tissue of the mucosa and sub- 
mucosa of the intestinal tract, as well as in the glandular organs ; rarely in the inter- 
muscular connective tissue. 

Mucous tissue may develop from any proliferating connective-tissue substance, but 
rarely appears in large masses, and is usually a transitory form passing over either into 
fat or connective tissue. 

Fat-tissue develops particularly in those regions normally containing fat, but oc- 
curs also at times in other places, for example, in the reticular connective tissue of 
atrophic lymph-glands, in the perimysium internum of atrophic muscles, etc. 

The close relationship of the connective-tissue substances to each other enables the 
different forms to pass from one to another without the need of an intermediate stage 
of embryonic tissue produced by proliferation. Further details in regard to this point 
are contained in the next part. 

Literature. 

New-formation of Connective-tissue and Elastic Fibres. ) 

Beltzow: Regeneration der Sehnen. Arch. f. mikr. Anat., xxii. 
Busse: Heiiung asept, Wunde der Haut. Virch. Arch., 184 Bd., 1893. 
Dmitrijejff: Verand. d. elastischen Gewebes b. Arteriosklerose. Beitr. v. Ziegler,, 
xxii., 1897. 

Fischer: Exper. Unters. lib. d. Heiiung von Schnittwunden d. Haut. Inaug.-Diss., 
Tubingen, 1888. 

riemming-: Z. Entwickelungsgesch. d. Bindegewebsfibrillen. Festschr. f. Virch., i.,. 
Berlin, 1891. 

Gardner: Histogenese d. elastischen Gewebes. Biol. Cbl., xvii., 1897. 
Graser : Feinere Vorgange bei Verwachsung peritonealer Blatter. Zeit. f . Chir., xxvii., 
1888. 

Haasler: Regenerat. d. Rlickenmarks. Arch. f. klin. Chir., 1., 1895. 
Hamilton: On the Presence of New Elastic Fibres in Tumors. Trans. Chicago, Path. 
Soc, 1900. 

Hansen: Genese einiger Bindegewebsgrundsubstanzen. Anat. Anz., xvi., 1899. 
Homen: Regeneration der fix en Hornhautzellen. Fortschr. d. Med., i., 1883. 
Jores: Neubildung elast. Fasern. Beitr. v. Ziegler, xxiv., 1898; xxvii., 1900. 
Klemensiewicz : Karyokinese in den fixen Hornhautzellen. Cbl. f. d. med. Wiss., 
1884. 

Kromayer: Regen. d, elast. Fasern in Hautnarben. Monatsh. f. Derm., xix., 1895. 
liwoff: Entwickelung d. Fibrillen des Bindegew^ebes. Wiener Sitzber., 98 Bd., 1889. 
Melnikow: Unters. lib. d. elastischen Gewebe. Beitr. v. Ziegler., xxvi., 1899. 
Merkel: Histogenese d. Bindegewebes. Verb. d. Anat. Gesellsch., v., 1896. 
Neelsenu. Angelucci: Untersuch. iiber Keratoplastik. Klin. Monatsbl. f. Augenhk.,. 
1880. 

Neumann: Entwickelung d. Bindegewebes in pleuritisclien Schwarten. Arch. d. 
Heilk., 1869. 

Nikiforoff: Bau u. Entwickelung des Granulationsgewebes. Beitr. v. Ziegler, viii., 
1890. 

Oliver: Elastic Tissue in Cirrhosis of the Liver. Trans. Chicago Path. Soc, 1902. 
Passarge u. Krdsing: Regen. d. elast. Gew. d. Haut. Derm. Stud. v. Unna, xviii., 
1894. 

Pearce: The Increase of Elastic Tissue in the Lung in Chronic Congestion, Jour, of 
Med. Res., 1901. 

Podwyssozki: Regeneration der Driisengewebe. Beitr. v. Ziegler, i., ii., 1886-87. 
Poljakoff: Anat. d. Bindegewebes. Arch. f. mikr. Anat., 45 Bd., 1895. 
B-anvier: Mecanisme de la cicatrisat. Lab. d'histol. du College de France, 1900. 
Spuler: Histogenese der Bindesubstanz. Anat. Hefte, xxi., Wiesbaden, 1896. 
Stroebe: Heiiung von Riickenmarkswunden. Beitr. v. Ziegler, xv., 1894. 
Tillmanns: Exp. u. anat. Unters. iiber Wunden der Leber u. Niere. Virch. Arch., 
78 Bd., 1879. 



292 



THE PROGRESSIVE CHANGES. 



Yamagiva: Zellenstudien an sich regenerirendem Sehnengewebe. Virch. Arch., 135 
Bd., 1894. 

Zachariades : Tissu coujonct. Lab. d'histol. du College de France, 1900. 
Ziegler: Untersuch. liber pathol. Bindegewebs- u. Gefitssneubilduug, Wurzburg, 1876. 
See also Inflammatory New-formations of Tissue. 

{New -formation of Cartilage. ) 
Bardeleben: Knorpel. Eulenburg's Realencj^klop., 1896. 

Ewetzky: Entzlindimgsversuclie am Knorpel. Arb. a. d. pathol. Instit. in Zurich. , 
iii., Leipzig, 1875. 

Gies: Heilung v. Knorpelwunden. Deut. Zeitschr. f. Chir., xviii., 1882. 
Kassowitz; Die normale Ossification, etc., Wien, 1881. 

Peyrand: Etudes exper. sur. la regen. des tissus cartilagineux et osseux, 1869. 
Schleieher: (Knorpelzelltheilung.) Arch. f. mikr. Anat., xvi. 
Schottelius: Die Kehlkopfknorpel, Wiesbaden, 1879. 

Sieveking: Wachstlium u. Regen. d. Knorpels. Morph. Arbeiten v. Schwalbe, ii., 
1891. 

Solg-er: Ueber Knorpelwachsthum. Fortschr. d. Med., vii., 1889. 

Spuler: Bau u. Entstehung d. elast. Knorpels. Inaug. Diss., Erlangen, 1895. (Lit.) 

{New formation of Bone, ) 

Barth: Knochenimplantation. Beitr. v. Ziegler, xvii., 1895. 

Bonome: Knochenregeneration. Virch. Arch., 100 Bd., 1885. 

Bruns: Die Lehre v. d. Knochenbriichen. Deut. Chir., Lief. 27, Stuttgart, 1886. 

Busch.: Knochenneubildung. Deut. Zeit. f. Chir., viii. ; Arch, f, klin. Chir,, xxi., 1877. 

Kassowitz: Die normale Ossification, etc., Wien, 1881, 1882. 

Kolliker: Die normale Resorption des Knochengewebes, Leipzig, 1872; Gewebelehre, 
1889. 

Krafft: Zur Histogenese des periostal. Callus. Beitr. v. Ziegler, i., 1886. 
Steudner: Beitrage zur Lehre von der Knochenentwickelung, Halle, 1875. 
Strelzoff: Die Histogenese der Knochen. Unters. a. d. pathol. Listitut in Zurich, 1873. 
Troja: Experiences sur la regeneration des os, Paris, 1890. 

Wolff: Unters. lib. d. Entwickelung d. Knochengewebes, Leipzig, 1874; Virch. 
Arch., 101 Bd., 1885. 

Ziegler: Proliferation, Metaplasie u. Resorption d. Knochengewebes. Virch. Arch., 
73 Bd., 1878. 

See also Pathological Anatomy of the Bones. 

( Formation of Lymphadenoid Tissue and Spleen-tissue. ) 

Bayer: Regeneration u. Neubildung der Lymphdrlisen. Prager Zeitschr, f. Heilk., 

vi.. 1885; Ueber kranke Lymphdriisen. Langenbeck's Arch., 49 Bd., 1895. 
Ceresole: Regeneration de la rate. Beitr. v. Ziegler, xvii., 1895. 

Czermack: Entwickelung d. Lymphnotchen d. Darmwand. Arch. f. mikr. Anat., 42 
Bd., 1893. 

Galland: The Development of Lymphatic Glands. Jour, of Path., ii., London, 1894. 
Laudenbach : Totale Milzregeneration. Virch. Arch., 141 Bd., 1895. 
Ribbert: Regeneration u. Entziindung der Lymphkdrlisen. Beitr. v. Ziegler, vi., 
1889. 

Saxer: Entwickelung d. Lymphdriisen. Anat. Hefte, Wiesbaden, 1896. 

Stohr: Die Enwickelung des adenoiden Gewebes. Anat. Anz., vi., 1891; Entwick- 
elung der Darmlymphknotchen. Arch. f. mikr. Anat., 41 Bd., 1898. 

Warthin : The Changes Produced in the Hoemolymph Nodes of the Sheep by Splenec- 
tomy Jour, of Med. Res., 1902; The Relation of the Hsemolymph Nodes to Adi- 
pose Tissue. Trans. Phil. Path. Soc, 1903. 

Zehnder: Ueber regenerative Neubildung der Lymphdriisen. Virch. Arch., 120 Bd., 
1890. 

§ 85. The new=forination of the white blood=cells occurs, in the first 
place, within the lymphadenoid tissue of the lymph -glands, spleen, and 
the intestinal tract, and there are contained within the lymph-nodes 
areas sharply outlined from their surroundings, in which there are 



NEW-FORMATION OF RED BLOOD-CELLS. 



293 



always present numerous cell-division figures which belong for the most 
part to free cells. These areas have been designated germ-centres (Flem- 
ming). Further, leucocytes are also produced in the bone-marrow and 
gain entrance to the blood through the vessels of the marrow. Moreover, 
division of leucocytes occurs in the lymj^h-vessels of the lymph-glands 
and the tissues, and there is now no doubt that leucocytes may divide in 
the circulating blood and in the tissue -spaces. Whether there may arise 
from the proliferation of connective-tissue cells such forms of cells as 
have the power of wandering into the blood-vessels, and which there 
may be regarded as white blood-corpuscles, is not yet settled. 

The division occurs chiefly through mitosis ; but amitotic division also 
takes place, and upon this phenomenon depends the fact that a large 
part of the leucocytes contain peculiar lobulated, wreath-shaped nuclei 
or even nuclei which have broken up into small fragments. 

Mitotic division is the form of division which leads to the formation 
of viable cells. In how far amitotic division (fragmentation of the nu- 
cleus) is followed by a cell-division is a diffi- 
cult question to decide, but it is to be as- ^ ^^^^ 
sumed that leucocytes with fragmented nuclei 
represent elements undergoing a retrograde ^^^iJA 
change. Consequently the transformation f ^ ^ 
of mononuclear into polynuclear leucocytes 



is to be taken as an evidence of approach- '^|®/^ 
ing dissolution. 4iJg^'%^ 

The new=formation of red blood=cells \* 
takes place (Bizzozero, ^^"eumann, Flemming) 
through mitotic division of nucleated young 
forms of red blood- cells, the erythroblasts. 
In the human adult this process is limited 

to the bone-marrow, and the same is true in i^o.-section from the germi- 

the case Ot mammals, birds, reptiles, and nalcentreof a mesenteric gland (after 

the tailless amphibia, while in the tailed am- c^^?e"?Sary2mSe^^^ 
phibia and in fishes the spleen also takes part ^^^^^^^ ZoniSZg''Sv'^ne 

in the formation of red cells. In embryos nucleus '"tingiwe bodies" and smaii 
the formation and multiplication of red cells J?Ec?ruXSwT'x'm 
occurs throughout the entire vascular sys- 
tem ; later this activity is confined to the spleen, liver, and bone-marrow, 
and finally to the last alone. 

^^'eumann holds that the multiplication of the young forms of the red 
cells occurs in the lymphoid marrow. According to Bizzozero and 
Denys the increase, under normal conditions, takes place only in the 
vessels of the marrow, and the complete development of the red cells is 
carried out in the same location. The change of the nucleated cells into 
the non-nucleated is brought about, according to the majority of ob- 
servers, by the disappearance of the nucleus. According to Eindfleisch, 
Howell, Malassez, and Maximo w the nucleus is extruded from the cell. 
According to Maximow there may be distinguished in the protoplasm of 
erythroblasts possessing old pyknotic nuclei, a granular substance lying 
close to the nucleus and a homogeneous peripheral substance. After the 
extrusion of the nucleus the inner granular substance, which stains with 
neutral red and other stains, remains preserved for a time, but vanishes 
during the ripening of the red blood-cells. 

The origin of the nucleated red cells has not yet been satisfactorily 
explained. According to Bizzozero the young forms of the red cells are 




294 



THE PROGRESSIVE CHANGES. 



of 9j peculiar type which constantly contain haemoglobin and have no 
colorless antecedents. Denys, Lowit, Howell, and Pappenheim hold, on 
the contrary", that they arise from nucleated, colorless cells containing no 
haemoglobin (basophile leucocj^tes according to Pappenheim), which ac- 
cording to Denys increase within the marrow- vessels ; while Lowit, on 
the other hand, holds that the colorless antecedents of the red cells, 
dividing by mitosis, and which he calls erythroblasts, occur in the 
lymi)h -glands and spleen, as well as in the bone-marrow, and are found 
both within the vessels and in the meshes of the reticular tissue. 

Flemming, who agrees with Bizzozero concerning the h(emoglobin 
content of the nucleated young red cells, is inclined to assume that the 
3'oung forms present in later life are direct descendants of the young 
forms of the embryonic period, ^^eumann holds that this hypothesis is 
not sufficient to explain all the phenomena of later life ; as, for example, 
the replacement of fatty marrow, which contains no nucleated red cells, 
by blood-forming lymphoid marrow, and the formation of blood-cells in 
newly developed marrow. He finds himself driven to the assumption 
that either a development of the nucleated red blood-cells takes place 
from the leucocytes of the blood which are carried to the marrow after 
birth by the arteries, or that they arise from the tissue-elements of the 
bone -marrow. 

In case of an increased formation of red cells, as occurring after loss 
of blood, and also in severe chronic anaemia and leukaemia, nucleated 
red cells may appear also in the circulating blood outside of the bone- 
marrow, while under normal conditions they are not found there. The 
fatty marrow acquires in such cases the character of lymphoid marrow, 
and this change is brought about by the disappearance of the fat through 
dilatation of the vessels with increased supply of blood, and through an 
increase in both the colorless and red cells of the marrow. 

Elirlicli {Zeitsclir. f. klin. 3Ied.,i.; C ha rite Anna!., ISS-i- YerMiidlung d. Pltys, 
Ges. z a Berlin, 1878-T'9; Beutscli. med. WocheiiscJir., and Ein horn ("Ueber d. Ver- 

halten der Lymphoc3'ten zii den weisseu Blutkorperclien," Inaiig.-Diss., Berlin, 1884, 
ref. FortscJir. der Med., iii.) distinguish among the leucocytes of the normal blood: (1) 
small lymj)hocytes with deeply staining nuclei of relatively large size, and with little 
jirotoplasm; (2) large lympliocytisv^iih large nuclei that stain lightly and with abundant 
protoplasm; {o) mononudeor fnn^.sitio/ud forms with irregular nuclei; (4) jjoly nuclear 
neutrophile leucocytes with polymorphous nuclei or with several nuclei, and containing 
neutrophile granules (grannies Avhich stain with a neutral dye, obtained by mixing acid 
f nchsin with basic methyl-green), these forming about seventh" per cent of all the white 
cells of the blood, and migrating in purulent inflammations; (5) eosinophile cells, Avhose 
protoplasm contains numerous granules staining with acid dyes (eosin); (6) mast-cells 
(0.5 per cent of the white cells) having basophile granulation. 

Loicit distinguishes among the colorless cells of the blood two different forms which 
he designates leucoblasts and erythroblasts, and which he believes to have a wholly 
different signiticance and not to pass over from one form to the other. The leucoblasts 
are the Ijmiphocytes Avith chromatin arranged in clumps, which do not undergo mitotic 
division, but pass over into the polynuclear leucocytes through fragmentation of the 
nucleus. The erythroblasts are the colorless young forms of the red cells. Avhich divide 
by mitosis, and are distinguished from the lymphoid cells by their homogeneous char- 
acter and slight contractilitv of the protoplasm. The transformation into haemoglobin- 
containing cells occurs partly in the blood, and partly in the bone-marrow. 

Flernming regards LoinVs vieAvs as incorrect, claiming that the observations of the 
latter give no eAidence of a transformation of colorless erythroblasts into red cells, and 
that leucocytes Avhich do not become changed into red cells also divide by mitosis. 
Neumann also is unable to agree Avith Loicit. 

Howell holds that the bone-marrow^ contains numerous colorless erythroblasts, 
which change in the marroAv into nucleated cells which later through the extrusion of 
the nucleus are transformed into non-nucleated red blood-cells. 

Petrone believes that the red blood-cells of the mammals are only apparently non- 



NEW-FORMATION OF RED AND WHITE BLOOD-CELLS. 295 



nucleated, and that it is possible b}^ means of especial methods of fixation and staining 
to render the nucleus visible. Negri has likewise found similar structures in red cells, 
but does not believe them to be nuclei. Malassez believes that the red cells arise from 
buds of nuclciited cells of the marrow. According to Benys, with whom E. R. Ziegler 
agrees, the red blood-cells have a peculiar origin ; and in birds are formed from the wall 
of the venous capillaries of the bone-marrow, which have a germinal layer of red blood- 
cells in the form of a cellular coating of m'dny layers, which give off into the blood- 
stream cells, wdiich then come to contain haemoglobin. 



Literature. 

{Neiv -formation of Leucocytes. ) 

Arnold: Theilungsvorgange an Wanderzellen. Arch. f. mikr. Anat., 80 Bd., 1887; 

Knochenmarkzellen. Virch. Arch., 144 Bd., 1896. 
Bizzozero: Bau d. Knochenmarks bei Vogeln. Arch. f. mikr. Anat., 85 Bd., 1890; 

Arch. ital. de Biol., xiv., 1890. 
Dekhuyzen: Mitosen in frei ini Bindegewebe gelegenen Leukocyten. Anat. Anz., 

vi. , 1891. 

Denys: La structure de la moc^Ue des os. La Cellule, iv., 1887. 

Drews: Zellvermehrung in der Tonsilla palatina. Arch. f. mikr. Anat., 24 Bd., 1885. 
Ehrlich u. Lazarus: Die Anilmie, i., Wien, 1898. 

Flemming': Zellvermehrung in Lymphdriisen, Tlieilungsarten der Leukocyten. Arch, 
f. mikr. Anat., 24 Bd., 1885 ; Theilung u. Kernformen bei Leukocvten. lb., 37 Bd., 
1891. 

Hayem: Du sang et de ses alterations organiques, Paris, 1889. 
Joas: Ueber eutziindliche Leukocytose. Beitr. v. Ziegler, x., 1891. 
Jolly: Diff. types de glob, blancs. Lab. d'hist. du Coll. de France, 1900. 
Lawdowsky : Unters. einiger Lebensvorgiinge des Blutes, Virch. Arch,, 96 Bd., 1884. 
V. Limbeck- Klin. Pathologic des Blutes, Jena, 1896. 

Lowit: ISTeubildung u. Zerfall weisser Blutkorperchen. Sitzber. d. K. Akad. d. Wiss. 

in Wien, 92 Bd., 1885; Anat. Anz., i., 1886; Neubildung u. Beschaffenlieit d. 

weissen Blutkorperchen. Beitr. v. Ziegler, x., 1891; Die Anordnung von Leuko- 

blasten u. Erythroblasten in d. Blutzeflen bildendeii Organen. x\nat. Anz., vi., 

1891; Arch. f. mikr. Anat., 88 Bd., 1891. 
Maurel: Rech. ex perimen tales sur les leucocytes, Paris, 1891. 
Mobius: Zellvermehrung in der Milz. Arch. f. mikr. Anat., 24 Bd., 1885. 
Miiller: Zur Frage der Blutbildung. Wien. Sitzber., 1889; Zur Leukamiefrage. 

Deut. Arch. f. klin. Med., 48 Bd., 1891; Mitose an eosinophilen Zellen. Arch. f. 

exp. Path., 29 Bd.', 1891. 
Neumann. Bed. d. Knochenmarks fiir die Blutbildung. Centralbl. f. d. med. Wiss., 

1868; Arch. d. Heilk., X., 1869. 
Oppel: Die Entsteliung der rotlien u. weissen Blutkorperchen. Cbl. f. allg. Path., 

1892 (Lit.) 

Pappenheim: Bez. d. farblosen Blutkorperchen, zu einander. Virch. Arch., 160 Bd., 
1900. 

Paulsen. Zellvermehrung in Lymphdriisen u. Tonsillen. Arch. f. mikr. Anat., 24 
Bd., 1885. 

Roemer : Formativer Reiz der Proteine Buchner's auf Leukocyten. Berl. klin, Woch., 
1891. 

Saxer: Abstammung d. w^eissen u. rothen Blutkorper von primaren Wanderzellen. 

Cbl. f. allg. Pathol., vii., 1896. 
Schedel: Zellvermehrung in der Thymus. Arch. f. mikr. Anat., 24 Bd., 1883. 
Spronck; Regeneratie van Leukocyten in het circuleerende Bloed. Fortschr. d. Med., 

vii. , 1889. 

Zenoni: Entsteliung versch. Leukocytenformen. Beitr. v. Ziegler, xvi., 1894. 

{Formation of Bed Blood-cells). 

Arnold; Hamoglobinlialtige Knochenmarkzellen. Virch. Arch., 144 Bd., 1896. 
Bizzozero Gaz. Med. Lombarda, 1869, No. 2; Centralbl. f. d. med. Wissensch., 1869, 

1880, 1881; Arch, der le Sc. Med., iv. ; Arch, itah de Biol, i., iv., xiv.; Virch. 

Arch,, 95 Bd ; Bau des Knochenmarks bei Vogeln. Arch. f. mikr. Anat., 35 Bd., 

1890. 

Bizzozero u Torre Entstehung d. rothen Blutkorp. Virch. Arch., 95 Bd., 1884. 
Cadet Etude physiolog. des elements figures du sang. These de Paris, 1881. 



296 



THE PROGRESSIVE CHANGES. 



Denys: La gen^se dii sang chez les oiseaiix. La Cellule, iv., Lou vain, 1888. 
Eberth.: Ueber die VennebruDg der rotlien Blutkorper. Fortscbr. d. Med , iii,, 1885. 
Ehrlich. u. Lazarus: Die Auaniie, 1., Wieii, 1898. 

Engel: Embrvon. rotbe BJutkorp. Arcb. f. mikr. Anat., 52 Bd., 1898; 54 Bd., 1899; 

Fortsehr. d. Med., xvi., 1898. 
Feuerstack: Eutwickelung d. r. Blutkorpercbeu. Zeitscbr. f. wiss. Zool , xxxviii , 

1883. 

Flemming": Zellsubstanz, Kern- n. Zelltbeiluug, 1882; L'eber Tbeilung und Kern- 

formeu bei Leukocvten. Arcb. f. mikr. Anat., 37 Bd., 1891. 
Hayem: Du sang et de ses alterations, Paris, 1889. 

Howell: Tbe Life History of tbe Formed Elements of Blood. Jour, of Morpb., iv., 

Boston. 1890, ref. Cbl. 1 allg. Patb., ii. 
Israel u. Pappenbeim : Entkernung d. Erjtbroblasten. Yircb. Arcb., 143 Bd., 1896. 
Kuborn: Devel. des vaisseanx et du sang dans le foie de I'embrj'on. Anat. Anz., v., 

1890. 

Ldwit: Wiener akad. Sitzungsber., 88 Bd., 1883; 92 Bd., 1885; 95 Bd., 1887. 
Malassez: Gaz. nied. de Pads, 1874 and 1878; Arcb. de pbys., ix., 1882. 
Maximow: Structur u. Entkernung d. r. Blutkorp. Arcb. f. Anat., 1899. 
Mondino: Sulla genesi des'li elementi del sangue, Palermo, 1888; Arcb. ital. de Biol., 
xii., 1889. 

Mosso: Umwandlung d. rotben Blutkorpercbeu in Leukocvt-en. Yircb Arcb., 100 
Bd., 1887 

K"egri: Persistenz des Kernes r. Blutkorp. Anat. Anz.. xvi., 1899. 

IMeumann: Bedeutung des Knocbenmarks fur d. Blutbildung. Cbl. f. d. med. Wiss., 

1868j 1869; Arcb. d. Heilk., xv. ; Arcb. f. mikr. Anat., xi. ; Entwickelung rotber 

Blutkorpercbeu im neuo-ebild. Knocbenmark. Yircb. Arcb., 119 Bd., 1890; Blut 

bildung b. Froscben. lb., 143 Bd.. 1896. 
Oppel: Die Entstebuno- rotber u. weisser Blutkorpercbeu. Cbl. f. allg. Patb., 1892 

(Lit.y 

Pcppenheim: Entwickelung d. Erytbroblasten. Yircb. Arcb., 145 Bd., 1896 (Lit.); 

Eutsteliung d. rotben Blutzellen.' Vircb. Arcb., 151 Bd., 1898. 
Petrone: L'esistenza del nucleo uell' emasia adulta dei mamniiferi, Catania, 1897; 

L'apparenze di cellule nel globulo rosso. Bull, dell' Accad. di. Sc. Nat. in Catania, 

1900. 

Reinert: Die Zitblung der rotben Blutkorpercben, Leipzig, 1891. 
Rindfleisch.: Knocbenmark u. Blutbildung. Arcb. f. mikr. Anat., xvii.. 1879. 
Sanfelice: Genese des corp. rouges dans Ta mobile des os. Arcb. ital. de Biol., xiii., 
1890. 

Scbmidt: L'eber Blutzellenbildung in Leber u. Milz. Bcitr. v. Ziegler, xi., 1892. 
Spuler: Ueb. d. intracellulare Eutsteliung rotber Blutkorper. Arcb. f. mikr. Anat., 40 
Bd., 1892. 

Timofejewsky : Regenerat. d. rotben Blutkorpercbeu. Cbl. f. allg. Patb., vi., 1895. 
Tizzoni: Fonction bematopoetique de la rate. Arcb. ital. de Biol., i., 1882. 
Tracbetti: Glob, rossi ed emoglobina nelle anemie sperim. Arcb. per le Sc. Med., 
1896. 

Zieg-ler, E. H. : Entstebung d. Blutes d, TTirbeltbiere. Ber. d. Xaturf. Ges. zu Frei- 
burg, iv., 1889. 

§ 86. The new=formation of transversely striated muscle=fibres 

takes its start from portions of old muscle -fibres; and although, after 
iujury to a muscle, the intermuscular connective tissue may be excited 
to active x)roliferation, there is formed in conseciuence only connective 
tissue, or probably also the sarcolemma of new fibres, but never new con- 
tractile substance. 

The first signs of a formative activity of the muscle-fibres after injury 
appear in the muscle-nuclei, in that these become elongated and then 
divide into a varying number of fragments (Steudel, Xauwerck). Even 
on the second day there may occur mitotic division (Fig. 171, b) of the 
muscle -nuclei. This form of division seems to be the only way in which 
multiplication takes place, and under favorable conditions it occurs very 
actively after the second day. 

The behavior of the contractile substance of the muscle differs very 
markedly according to the nature and extent of the injury. In the case 



REGENERATION OF MUSCLE. 



297 



of traumatic, toxic, aud anaemic injuries it suffers a fragmentation into 
larger and smaller portions, so that the muscle-cells come to lie in spaces 
of varying size between the detritus of the muscle -fibres. Crushing and 
tearing can bring about a wide separation of the parts of the contractile 
substance. The ends of the pieces of muscle-fibres, in such a case, may 
be conical, oblique, transverse, or torn in an irregular edge, but not infre- 
quently after a short time the ends become split into two or more i)ointed 
filaments (Fig. 171, a). 

The mitotic division of the muscle-nucleus takes place, not only in 
nuclei that rest upon living fibres (a), but also in the muscle-cells lying 
free in the spaces between the separated muscle-fibres (h) ; and in l3oth 
places leads to the productiou of large multinuclear cells, which form 
multiuuclear protoplasmic masses on the ends of the muscle-fibres (e, f) 
as well as on the body of the fibres (c). Into these masses the trans- 



FlG. 171.— Portions of muscle-flbres showing regenerative proliferation, from museh^-wounds of dif- 
ferent ages (Flemming's, saf ranin) . a. Pointed ends of the split stump of a muscle-lloro, with nuclear divi- 
sion-figures, three days after laceration of the muscle ; proliferated muscle-nuclei transformed into cells 
rich in protoplasm, one of which is in process of mitotic division ; c, piece of a muscle-flbre eight days after 
tying the muscle ; d, giant-cells, enclosing necrotic pieces of muscle, from a muscle-scar twentv-slx days 
old; e, /, muscle-fibres ending in protoplasmic masses (muscle-buds), e, from a muscle-scar ten davs old, 
/, from one twenty-one days old ; g, dividing muscle-flbres from a muscle-scar forty-three days old. X 315. 



versely striated muscle -substance passes w ithout a sharp line of demarca- 
tion. There occurs, therefore, at the same time with the multiplication of 
the nuclei an increase of the sarcoplasrn of the muscle-fibres, and this becomes 
distincthj visible; it is probable also that muscle-fibrillse may become 
changed back into sarcoplasm. 

The muscle-cells not connected with living contractile substance be- 
come changed into large epithelioid cells tcith large nuclei (b). Tlirough 
continued division of the nucleus these cells become transformed into 
multinuclear protoplasmic masses (d) ; and a scar, consisting of prolifer- 
ating connective tissue, of from eight to thirty days old, contains such 
giant-cells which often enclose the remains of old muscle-fibres (d) in 
large numbers. 

The new muscle-fibres develop for the chief part from the richly nucleated 
sarcoplasm, which appears in the continuity and at the ends of the muscle- 
fibres, in connection with the formation of numerous large nuclei, and 
which through its increase of size causes an increase in the thickness and 
length of the muscles, which has been designated budding by Neumann. 




I 



1 



298 



THE PROGRESSIVE CHANGES. 



With the transformation of the sarcoplasm into muscle -fibrillae there 
appears gradually a longitudinal and later a transverse striation, a sign 
that the organic structure of the plasma has comx)leted its development 
in the way characteristic of muscle. 

The greater part of the jyrol if e rating muscle -cells icJiich Jia.ce no connection 
with living muscle-fibres die; but it is to be noted that they persist foi- a 
long time, so that not infrequently there may be seen in muscle-scars 
from eight to forty days old great numbers of i^rotoiDlasmic masses ver^^ 
rich in nuclei. Under certain circumstances these may form long, con- 
nected bands, or rows of separate pieces of protoplasm. There can be 
no doubt that a part of these cells under favorable conditions become 
transformed into transversely striated muscle-substance ; and this takes 
place either by the formation of new independent muscle -fibres or by 
union with old muscle-fibres or muscle-buds. The disconnected new- 
formation of muscle from proliferating muscle-cells occurs particularly 
when the contractile substance is destroyed while the sarcolemma remains 
intact (as in typhoid fever). On the other hand, the formation of buds 
is observed especially at the ends of fibres which have been divided. 

The buds springing from the ends or sides of muscle-fibres may cause 
a simple elongation of the muscle-fibre, frequently deviating from its 
original direction (/). Often there are seen fibres which have split into 
two or three parts (g), so that the old fibres branch as they pass into the 
muscle-scar. As far as we know, this splitting of the fibre occurs very 
early (a), before the proliferating muscle-nuclei have formed much sar- 
coplasm, so that the proliferation appears first in the split portions of 
the fibre. As a result of such splitting a muscle-scar may come to con- 
tain a greater number of muscle-fibres than were originally present in 
the affected area. 

Hypertropliy of transversely striated muscle takes place through an 
eirLargement of the indiA idual muscle -fibres ; the thin muscle-fibres in 
particular becoming increased in thickness (Mori:)urgo). The nuclei do 
not become increased in number. On the other hand, such an increase 
does take place in the case of a growth in length of the muscle ; and is 
the result, most probabl^^ of amitotic division (Mori^urgo). 

A new=formation of heart=muscle has not yet been positively demon- 
strated. After injuries of the heart, division figures appear in the mus- 
cle-cells, but after a few days these can no longer be demonstrated, and 
the wound heals through the formation of ordinary- scar-tissue. Focal 
degenerations of the my ocardium likewise heal by connective-tissue cica- 
trization. If through any reason the heart=muscle becomes hypertro= 
phied, the increase in size takes place through the enlargement of the 
muscle-cells ; whether an increase in the number of the cells also occurs 
is not yet known with certainty. 

A new=formation of smooth muscle=fibres as well as regeneration, 
occurs after traumatic or toxic and ischsemic degeneration. It occurs 
also in hypertrophic new-formations of muscle-tissue — for example, in 
tumors — and is initiated by mitotic division of the nuclei of the muscle- 
cells, which is followed by division of the cells. According to the results 
of experimental work and also of observations upon the muscle-tissues of 
man, the reproduction of fibres after injuries and focal degenerations is 
but slight, ceasing after a short period. Thus, for example, defects in 
the muscnlaris of the stomach and intestines or of the bladder are, for 
the chief part, closed only by connective tissue. 

Hypertrophy of smooth muscle=fibre is a phenomenon which, within 



REGENERATION OF NERVE-TISSUE. 



299 



certain limits, is of very frequent occurrence. In the pregnant uterus 
the size of the muscle-cells may reach five to ten times the ordinary size. 
Of other organs the bladder most frequently shows a marked hypertro- 
phy of smooth muscle. 

Literature. 

{Begeneration of Striped Muscle. ) 

Barfurth: Zur Kegeneration der Gewebe. Arch. f. mikr. Anat., 37 Bd., 1891. 
Dore : Dc la regen. du tissu muscul., etc., Paris, 1881. 

Felix: Wachstlium der quergestr. Musciilatur. Zeitschr. f. wiss. Zool., 48 Bd., 1889. 
Gal9otti 11. Levi: Regen. d. quergestr. Miiskels. Beitr. v. Ziegler, xiv., 1893. 
V. Kahlden: Regen. d. quergestr. Muskeln (Referat). Cbl. f. allg. Path., iv., 1898. 
Kirby: Unters. lib. Degeneration u. Regeneration d. Muskelgewebes. Beitr. v. Zieg- 
ler, xi., 1892. 
Kolliker: Gewebelehre des Menschen, i., 1889. 

Kraske: Unters. liber die Regeneration der quergestr. Muskelfasern, Halle, 1879. 
!Leven: Regeneration der quergestr. Muskelfasern. Deut. Arch. f. klin. Med., Ixiii., 
1888. 

Morpurgo: Ipcrtrofie funzionali dei muscoli. Arch, per le Sc. Med., xix., 1895; xxii., 
1898; Virch. Arch., 150 Bd., 1897; Kernwucherung beim Langenwachsthum. 
Anat. Anz., xvi., 1899. 

Nauwerck: Ueber Muskelregeneration nach Verletzungen, Jena, 1890. 

Neumann: Ueber den Heilungsprocess nach Muskelverletzungen. Arch. f. mikr. 
Anat., 1868. 

Panet: Die Entwickelung der quergestr. Muskeln aus Sarkoblasten, Wien, 1886. 
Robert: Wiederbildung quergestr. Muskelfasern. Beitr. v. Ziegler, x., 1891. 
SchafEer: Histol. u. Histogenese der quergestr. Muskelfasern, Wien, 1893. 
Steudel u. Nauwerck: Regeneration der quergestr. Musculatur. Beitr. v. Ziegler, 
ii., 1888. 

Valle: Rigeneraz. dei muscol. volont. Arch, per le Sc. Med., xxiv., 1900. 
Volkmann: Regeneration des quergestr. Muskelgewebes. Beitr. v. Ziegler, xii., 1893. 
Zaborowski: Regen. d. quergestr. Musk. Arch. f. exp. Path., xxv., 1889. 
Zenker. Ueber die Regen. des quergestr. Muskelgewebes, Leipzig, 1864. 

{Regeneration of Smooth Muscle, and of Heart-muscle.) 

Askanazy, S. : Ueber die Regeneration glatter Muskelfasern. Inaug.-Diss., I^onigs- 
berg, 1891. 

Aufrecht: Herzhypertrophie. Pathol. Mittheil, ii., Magdeburg, 1883. 
Berent: Heilung von Herzwunden. Inaug.-Diss., Konigsberg, 1892, 
Bonome: Heilung von Herzwunden. Beitr. v. Ziegler, v., 1889. 

Busachi: Ueber die Neubildung von glattem Muskelgewebe. Beitr. v. Ziegler, iv., 
1888. 

Goldenberg: Hypertrophic der Herzmuskeln. Virch. Arch., 103 Bd., 1886. 
Herczel: Muskelliypertrophie bei Darmstenosen. Zeitschr. f. klin. Med., xi., 1886. 
Jakimowitsch : Regen. glatter Muskeln. Cbl. f. d. med. Wiss., Wien, 1879, 
Kolliker: Gewebelehre des Menschen, i., 1889. 

Martinotti: Sugli effetti delle ferite del cuore. Giorn. della R. Accad. de Med. di 
Torino, 1880. 

Pog-g-i: La cicatrisation immediate des blessures de I'estomac. Beitr. v. Ziegler, iii., 
1888. 

RitscM: Heilung v. Wunden d. Magens, Darmkanals u. Uterus. Virch. Arch., 109 
Bd., 1887. 

Stilling- u. Pfitzner: Regen. glatter Muskeln. Arch. f. mikr. Anat., 28 Bd., 1886. 
Tangl: Hypertrophic des Herzens. Virch. Arch., 116 Bd., 1889. 

§ 87. Regenerative new=formation of the nerve=elements of the 
central nervous system through the new=formation of gangIion=cells 

most probably does not occur in man and mammals in post-embryonal 
life. According to the investigations of Stroebe, on the other hand, 
divided nerve -fhrils (in mammals) may grow lengthwise to a certain extent 



300 THE PROGRESSIVE CHANGES. 



through sprouting of the axis-cylinder; and this is true particularly of the 
fibres of the pyramidal tracts and the posterior roots, both of which 
after being divided grow into the scar-tissue developing at the site of the 
wound, the former in a downward direction, the latter upward. A com- 
plete restoration of nervous tissue does not take place, and a defect in 
the spinal cord due to trauma is replaced essentially by connective tis- 
sue, in part also by neuroglia. It is not yet known whether the loss of 
single nerve-fibres of the brain and spinal cord may under favorable 
conditions (preservation of the su]3porting tissue) be entirely restored 
through an outgrowth of the axis-cylinders. 

Regenerative and hypertrophic proliferations of neuroglia are phe- 
nomena which occur frequently in diseased conditions of the central 
nervous system, and either follow degenerative changes of the nervous 
elements, or in part also destruction of the neuroglia, or they may 

appear without such 
antecedents, in the 
latter case arising in 
part during the period 
of development. 

The new-forma- 
tion is brought about 
by mitotic division of 
the nuclei and cell- 
bodies of the glia- 
cells, eventuall}" also 
of the ependyma-cells. 

The newly formed 
glia- cells produce 
later a great profusion 
of delicate fibrillar 
processes (Fig. 172, 
a), and, as in the nor- 
mal tissues of the cen- 
tral nervous system, 
there may be distin- 
guished among these 
cells which are known as astrocytes (Deiter's cells) two varieties, the so- 
called mossy cells {Kurzstrahler) and the so-called spider -cells (Lang- 
strahler) with long, stiff, less-freely branching processes {a). The 
processes of these cells form sometimes a loose, sometimes a dense felt- 
work of fine fibrillse («, h) in which the cells, which have but little proto- 
jjlasm, are embedded. After full development of the tissue a separation 
of the processes from the cell-bodies may take place. The thickening 
of the tissue caused by the proliferation is known as sclerosis. 

Regenerative new=formation of the nerve=fibres of the peripheral 
nervous system is of very frequent occurrence and takes place in all 
those cases in which through any influence the continuity of a nerve- 
fibre is entirely or partially interrupted. For its accomplishment, how- 
ever, it is indeed necessary that the ganglion-cells v, hose i^rocesses form 
the nerve-fibres in question be preserved. 

When a nerve has been severed, the axis-cylinders and medullary 
sheaths, in the distal portion, undergo degeneration, the latter breaking 
up into drojj-like detritus, which later is dissolved. During the disin- 
tegration of the nerve-fibres the nuclei situated beneath the sheath of 




Fig. 172.— Sclerotic tissue from the posterior columns of a case of 
multiple sclerosis (Miiller's fluid, Mallory's method), a, Glia-cells with 
numerous processes, seen in longitudinal section; l», sclerotic tissue 
with transversely cut glia fibres. X 500. 



REGENERATION OF NERVES. 



301 




Schwann undergo mitotic division and form cells rich in protoplasm, 
which may take up into themselves the products of the destruction of 
the nerve-fibres. 

Of the proximal portion of the nerve the 
peripheral extremity alone degenerates, as 
far as the next Eanvier's node, or the next 
one beyond. 

The regeneration of the nerves begins a 
few days after the operation, in the proximal 
portion, about 0.4-2 cm. above the cut end. 

The first change consists in a swelling of 
individual axis-cjdinders in the peripheral 
parts of the nerve- bundle of the proximal 
end, which is later followed by a splitting- 
off of two to five or more new axis- cylinders. 
The new axis-cylinders arising in this way 
from the old ones grow in a longitudinal 
direction (Fig. 173, a, h) and form, within 
the sheath of Schvv^ann, whole bundles (Figs. 
173, c ; 174, e) of newly formed nerve-fibres, 
which for the most part fill up the entire 
lumen of the old nerve-tubes, and indeed 
stretch it, and more rarely enclose remains 
of the old fibres (Fig. 174, /). Single fibres 
may even break through the old sheath of 
Schwann, and then either extend further in 
the endoneurium, or penetrate through the 
perineurium of the nerve -bundle into the 
epineurium. 

In this way there are formed on the lower end of the proximal portion 
of the nerve a large number of new nerve-fibres, which in the beginning 

consist only of the newly formed axis- 
cylinders, but immediately surround 
themselves with a medallary sheath, 
which by reason of its irregular de- 
velopment gives to the nerve-fibres a 
varicose appearance (Fig. 174, c). 
Later the fibres acquire a neurilemma- 
sheath — that is, a connective-tissue 
covering which is probably formed 
from the nerve -corpuscles concerned in 
the proliferation. 

When a nerve is entirely severed 
and there is no possibility of a union 
with the distal portion — as, for ex- 
ample, occurs in all amputations of the 
extremities — there is forined in the re- 
gion of the cut end an embryonic tissue, 
vrr. nr.r. ^ f f u ^, springing from the connective tissue of 

iiG. 174.— Cross-section of a nerve-bundle , . , t , , 

of the median nerve just above a wound divid- the liervCS, whlCh later Oil bCCOmCS 

fiX^^'l^r^.^lCTfJl^^?-. chauged into connective tissue. In the 
d;'oM^°SnSic,%e"trb'r^re?ta„X^^^^ beginning free from nerves this con- 

newly formed nerve-fibres ; f, newly formed liective tissnc bcCOmCS penetrated bv 
nerves, with remains of old fibres inside the • j_ /? j i 

same sheath. X 200. youug uerves growing out from the 



Fig. 173.— Old and newly formed 
nerve-fibres from an amputation- 
stump, in longitudinal section (Miil- 
ler's fluid, Weigert's stain), a, Z), Old 
nerve-fibres, from which several young 
nerve-fibres have grown; c, neuri- 
lemma with young nerve-fibres. X 
180. 




302 



THE PROGRESSIVE CHANGES. 



nerve-fibres of the nerve-stump, wliicli, arranged in small bundles, or 
scattered, grow into the connective tissue and penetrate it in every direc- 
tion (Fig. 175). Not infrequently the growth of nerves is so extensive 
that nodular or clubbed swellings (Fig. 175, h) arise on the ends of the 
nerves. Such a swelling is known as an amputation-neuroma. 

When a nerve after division is again united, or if the division of the 
nerve is only partial, the nerve-fibres growing out from the proximal end 

after penetrating the connective tissue 
formed in the site of the wound, may in 
part, or all, find their way into the per- 
ipheral portion of the nerve where, in the 
mean time, the nerve-fibres have been de- 
stroyed. In this way the distal end may 
again become neurotized — that is, supplied 
by new nerves. According to investiga- 
tions of Forssmann, the direction of the 
newly growing fibres is governed by 
chemotactic influences arising from the 
disintegration -products of the old nerve- 
fibres. 

According to the investigations of 
Yanlair the growth of a regenerating 
nerve is about 0.2-1 mm. daily, accord- 
ing to the character of the tissue. A 
portion of the new nerve-fibres may pen- 
etrate into the old, empty sheath of 
Schwann ; others extend into the epineur- 
ium and perineurium, and in this situa- 
tion grow toward the periiDhery to the 
end -organ. Single fibres may pass by the 
end of the nerves, and grow toward the 
periphery, either along the old nerves or 
by an independent route. Many fibres, 
which leave the old route, are finally lost 
in the tissues. In the lower portion of 
the interinediate substance (Vanlair) the 
nerve- strands begin to separate into 
bundles again, and with the formation 
of a perineurium about the latter, the re- 
generated nerve takes on more and more 
the structure of a normal nerve. 

The above -described process of regen- 
eration requires for its accomplishment 
sometimes is not complete after several 




Fm. 175.— Amputation-neuroma of tlie 
sciatic nerve, in longitudinal section (am- 
putation of nerve nine years previously) 
(Miiller's fluid), a, Nerve; neuroma. 
X 3. 



weeks or 
months. 



even months, and 



The question of the regeneration of the central nervous system is still under 
discussion. It is generally accepted, as having been established beyond all doubt, that 
in the cold-blooded animals, reptiles, and tailed amphibia, a regenerative new-forma- 
gation of portions of the central nervous system can take place. In the case of warm- 
blooded animals, particularly in the mammals, the majority of experimental investi- 
gations have failed to demonstrate a regenerative new-formation of ganglion-cells. 
TedescJd, Vitzou and others, claim to have observed, after injuries of various kinds, 
both a new-formation of neuroglia and of ganglion-cells and nerve-fibres; but the 
investigations carried out in my laboratory by Tschistoioitsch seem to me to contradict 



REGENERATION OF NERVE TISSUE. 



303 



these assertions. The results obtained by Grunert in experimental work with pigeons 
agree with the conclusions arrived at by TscJiistoiDitsch. 

Monti and FiescM could demonstrate no evidences of regeneration in the ganglion- 
cells of the sympathetic after injuries. Torelli found only degenerative changes in 
the ganglion-cells of rlie intervertebral ganglion after injury of the same. 

The new=forniatiou of peripheral nerve=fibres has been made very frequently 
the subject of experimental research, and different observers have come to very differ- 
ent conclnsions (see titroebe, I. c. ). The above-described mode of new-formation I regard 
as firmly established, in so far as its essentials are concerned, upon the ground of per- 
sonal investigations. I have been unable to confirm the views of Aeuviann, Bobbert, 
Ddszkiciricz, Cattani, ^yeir Mitchell, Gluck, Beneke, toil Bilngner, Wieting, and others, 
who hold that the new fibres in the distal portion of the severed nerve rise autochthon- 
ously from tlie nuclei of the sheath of Schwann, or from the old axis-cylinder, or from 
a protoplasmic mass foi'med by a chemical transformation of the medullary sheath and 
axis-cylinders (^eunuiini-Bobbert). Likewise, the attempt made by JSeumanii and 
Wieting {Marchand) to bring into accord the established fact of the outgrowth of the 
axis-cylinders of the proximal portion into the scar uniting the severed ends, with the 
theory of the origin of new nerve-fibres from the nuclei of the sheath of Schwann, or 
from Uie remains of old fibres, or from both, by the assumption that the axis-cylinders 
growing from the proximal end convey a stimulus from the nerve- centres to the distal 
portion and thereby make possible the development of new fibres, I regard as unsuc- 
cessful, and hold to the above-given view. lam further of the opinion that the medul- 
lary sheath is not formed by the cells of the sheath of Schwann, but represents a product 
of the axis-cylinders; but further investigations as to this point are needed. According 
to JSissl, Mannesco, and others (see Barbacci, I. c.) there occurs, after the severing of a 
nerve, first a degeneration in the corresponding ganglion-cells with disintegration of 
the Nissl's bodies, and this may lead to the destrucdon of individual cells. Later, 
progressive changes with new-formation of chromatin take place, and may lead to 
hypertrophy of the cells (Mariiiesco); these changes reach their maximum in about 
ninety days, after which time thei'e is a return to the normal condition. 

The regenerative new=formation of the tissues of the eye has in recent years 
been repeatedly an object of research. According to Wolff, Midler, and Koclis the lens 
of tritoDS may regenerate, after removal, by means of a proliferation of the epithelium 
of the inner layer of the iris. According to Bijtliig, the same thing occurs in the trout. 
Gonin observed in rabbits, after the lens had been removed in such a manner that the 
capsule and some of the equatorial lenticular fibres and epithelium of the anterior wall 
were left behind, that there occurred a proliferation of this epithelium, leading to the 
union of the anterior and posterior walls through cells resembling connective-tissue 
cells. A new-formation of lenticular fibres from these cells does not take place. 
Remains of the lenticular fibres may form a rudimentary, useless lens, which in the 
case of young animals may become somewhat enlarged through the growth of the fibres. 
Randolph obtained somewhat better results in guinea-pigs. In the human eye .similar 
formations are seen after removal of the lens, and are known under the name of " Krys- 
tallwulst " {Baas). According to Franke, Krikkrnann, and Stoewer, the sclera possesses 
but slight power of proliferation. Wounds of the same are healed chiefly through 
proliferation of the choroid and episcleral tissue. 

According to Baquis, there occurs, in the injured retina of the rabbit, division of 
both ganglion and neuroepithelial cells. According to Krilckmann, the pigment- 
epithelium is capable of extensive regeneration, but neuroepithelium, on the other 
hand, is not again formed. 

Literature. 

{Regeneration of the Elements of the Central Nervous- System.) 

Barfurth: Zur Regeneration der Gewebe. Arch. f. mikr. Anat., 87 Bd., 1891. 
Caporaso . Rigenerazione del midoUo spinale della coda dei Tritoni. Beitr. v. Ziegler, 
v., 1889. 

Coen; Ueber die Heilung von Stichwunden des Gehirns. Beitr. v. Ziegler, ii., 1889. 
Dentan: Recli. sur la regeneration de la moe.Ue epiniere. Diss, in Berne, 1875. 
Eichhorst u Naunyn : Ueber die Regeneration u. Veranderungen im Rlickenmark 

nach streckenweiser totaler Zerstorung desselben. Arch. f. ex p. Path., ii., 1874. 
Friedmann : Progressive Veranderungen an den Ganglienzellen bei Entziindungen. 

Arch. f. Psych., xix., 1887; Zur Histologic der acuten Encephalitis. Neurol. Cbl., 

1889 

Grunert Regenerationsfahigkeit d. Gehirns. Arb. a. d. path. Inst. Tiibingen, ii., 



304 



THE PROGRESSIVE CHANGES. 



His: Histogenese u. Zusammcnhang d. Nervenelenieiite. Verb. d. X. intern, med. 
Congr., ii., Berlin, 1891; Die Neuroblasten u. dereu Eutsteliung im embryonalen 
Mark, Leipzig, 1889. 

Keresztszeghy ii. Hanns. Rejrenerationserscb. im Ruckenmark. Beitr. v. Ziegler, 
xii., 1892. 

Masius et Vanlair: Regen. d. Rlickenmarks bei Frosciien. Mem. de I'Ac. de Bel- 
gique, T. 21, 1870. 

Mondino: Sulla cariocinesi delle cellule nervose. Rend. R. Istituto, Loml:ardo, 1885. 
Monti et FiescM: Guerisou des bless, des ganglions sympatbiques. Arcb. ital. de 
Biol., xxiii., 1895. 

Miiller, H. : Regen. d. Wirbelsaule u. d. Rlickenmarks v. Eidecbsen w. Fiscben, 
Fi-ankfurt, 1864. 

Sanarelli: Les proc. de reparat. dans le cerveau et dans le cervelet. Arcb. ital. de 
Biol., xiii. 

S chieflFer decker : Ueb. Reg., Deg. u. Arcbitektur d. Rlickenmarks. Vircb. Arcb., 67 
Bd., 1876. 

Stroebe: Heilungv. Ruckenmarkswunden. Beitr. v. Ziegler, xv., 1894; Histol. d. de- 
gen, u. regen. Processe im centralen Nervensyslem. Cbl. f. allg. Patb., 1895 
(Lit.). 

Sgobbo: SuUe rigen. del midoUo spinale. La Psicbiatria, viii., 1891. 
Tedeschi: Regen. d. Gewebe d. Centralnervensj'stems. Beitr. v. Ziegler, xxi., 1897, 
Tirelli: Proc. repar. dans le ganglion intervertebral. Arcb. ital. de Biol., xxiii.. 1895. 
Vitzou: La neoform. des cell, nerveuses dans le cerv. du singe. Arcb. de pbys., ix., 
1897. 

(Eegeneration of the FeiHpkefal Nerves. ) 

Barbacci: Die Xervenzellen (Verand. nacb Nervendurcbscbneid ). Cbl. f. a. Patb., x., 
1899 (Lit.). 

Beidl: Verb. d. Nerven u. ibrer Centren nacb Durcbscbneidung. Wien. klin. Wocb,, 
1897. 

V. Biing-ner: Regeneratioasvorgange an Nerven nacb Yerletzuugen. Beitr, v. Ziegler, 
x., 1891. 

Cattani: Sulla deg. e neoformaz. delle fibre nervose. Arcb. per le Sc. Med , xi,, 
1887. 

Demoor: Contrib. a I'etude de la fibre nerveuse, Bruxelles, 1891. 

Eichhorst: Leber Nervendegeneration u. Regeneration. Vircb. Arcb., 59 Bd., 1874. 
Forssmann; Lrsache der Waclistbumsricbtung d. peripb. Nervenfasern. Beitr. v. 

Ziegler, xxiv., 1898; Neurotropismus. lb., xxvii., 1900. 
Galeotti u. Levi: iS'eubildungen nerv. Elem. im regen. Muskelgewebe. Beitr. v. 

Ziegler, xvii., 1895 (Lit.). 
Gessler: Die motoriscben Endplatten, Leipzig, 1885. 

His: Histoijeuese u. Zusammenbang d. Nervenelemente. X. intern, med. Congr., ii.,. 
Berlin, 1891. 

Huber: A Study of tbe Operative Treatment for Loss of Nerve Substance in Peripberal 

Nerves. Jour, of Morjili., vol. xi., 1895. 
Kolster: Regen. durcbscbn. Xerven. Arcb. f. mikr. Anat.,41 Bd., 1893; Histogenese 

und Regen. peripb. Nervenfasern. Beitr. v. Ziegler, xxvi., 1899. 
Laveran: Recb. exper, sur la regeneration des nerfs, Strasbourg, 1867. 
Marinesco: Patb. gener. de la cellule nerveuse. La Presse med., 1897. 
Neumann: Degeneration u. Regeneration nacb Nervendurcbsclmeidung. Arcb. d. 

Heilk., ix., 1868; Kervenquetscbung u. Kervenreireneralion. Arcb. f. mikr. 

Auat.. .wiii., 1880; Axeiicy iindertropfen. Vircb. Arcb., 1-58 Bd.. 1898. 
Nissl: Verand, d. Ganglienz. d. Fac, nacb Ausreissung d. Nerven. A. Zeit. f. Psycb., 

48 Bd. 

V. Notthafft : Regenerationsprocesse am verletzt. peripb. Kerven. Zeit. f. wi.ss. Zool., 
o.-) Bd., 1893. 

Peterson: Peripberal Nerve Transplantation. Amer. Jour, of Med. Sc., 1899. 

Ranvier: Lemons sur I'bistologie du sj'st. nerveux, Paris. 1878. 

Santi Sirena: Ricercbe sperim. sulla riproduz. d. nervi, Palermo, 1880. 

Stroebe: Degeneration u. Regeneration peripb. Nerven, Beitr. v. Ziegler, xiii.. 1893; 

Cbl. f. allg. Patb., vi., 1895 (Zusfass, Ref. ilb, Regen, d. Nerven u. d. Endap- 

parate). 

Tillmanns: Leber Nervenverletzung u. Nervennabt. Arcb. f. klin. Cbir., xxvii., 
1881. 

Tizzoni: Sulla patol. del tessuto nervoso. Arcb. per le Sc. Med., iii., 1879. 
Vanlair: Arcb. de biol. de van Beneden et van Bambeke, 1882-85; Arcb de pbys., x.. 



TRANSPLANTATION AND IMPLANTATION. 



305 



1882; vi., 1885; viii., 188G; Compt. rend, de I'Acad. des sciences, 1885; Sur I'in- 
nervat. iudirecte de la peau. lb., 188C; De I'organisat. des drains de caoutchouc, 
etc. Revue de Cliir., 1886; La suture des nerfs, Bruxelles, 1889; La persistance de 
I'aptitude regeneratrice des nerfs. Bull, de I'Acad. Roy. de Belgique, 1888; Rech. 
clironometriques sur la regen. des nerfs. Arch, de phys., vi., 1894. 

Vulpian: Note sur la regen. dite autogenique des nerfs. Arch, de phy., i., 1874. 

Wieting"; Regen. periph. Nerven. Beitr. v. Ziegler, xxiii., 1898. 

Wolberg: Nervennaht. Deut. Zeitschr. f. Chir., xviii. and nix., 1883. 

{^Regeneration of the Tissues of the Eye. ) 

Baas: Linsenregeneration. Milnch. med. Woch., 1899. 
Baquis: f^tude exper. sur les retinites. Beitr. v. Ziegler, vi., 1888. 
Coluzzi: Rigen. parziale dell' occhio nei tritoni. Mem. Ace, Bologna, i., 1891. 
Fischel: Regen. d. Linse. Anat. Anz., xiv., 1898. 
Gonin: Regen. du cristallin. Beitr. v. Ziegler, xix., 1896 (Lit.). 
Kochs: Regen. d. Organe bei Amphibien. Arch. f. mikr. Anat., 49 Bd., 1897. 
Kriickmann: Pigmentzellen der Retina. Arch. f. Ophthalni., 48 Bd., 1899. 
Mliller; Regen. der Linse bei Tritonen. Arch. f. mikr. Anat., 48 Bd., 1896. 
Randolph: The Regeneration of the Crystalline Lens. Johns Hopkins Hosp. Rep., 
ix., 1900. 

Stoewer: Heilungsvorg. bei Wunden d. Auges. Arch. f. Ophthalm., 46 Bd., 1899. 
"Wolff: Linsenregeneration bei Tritonen. Biol. Cbl., xiv., 1896 ; An. Anz., xviii., 1900. 



III. The Results of Transplantation and Implantation of Tissues and 

Organs. 

§ 88. The local regeneration of tissue is, as mentioned in the last part, 
very often but slight, so that losses of tissue may be followed by perma- 
nent defects, and in place of the original structures there may a^Dpear 
only a cicatricial tissue of a lesser value. Consequently, from practical 
reasons, many attempts have been made, through transplantation and 
implantation of tissue, to aid and to improve the healing -process ; and 
such attempts have in part been successful. At the same time they have 
also thrown light upon the individual life of the tissues and upon the 
behavior of the organism toward implanted living tissue. 

The most successful results have been obtained in the transplantation 
of tissues ichieh remain connected with their nutrient vessels, since the same, 
at the point of union between the transplanted portion and the under- 
lying tissues upon which it is placed, grow together with the latter in 
essentially the same manner as do the edges of the wound in the case of a 
cut. This method is utilized most frequently in the case of plastic oper- 
ations upon the surface of the body, but it finds application also in inter- 
nal surgery. For example, wounds of the bladder, intestine, ureters, 
tubes, etc., may be easily closed through implantation of the omentum; 
and the surface presenting upon the lumen of the organ concerned 
becomes very quickly covered over by the neighboring epithelium, which 
extends over it from the edges, or is also transplanted from the opposite 
epithelial surface (Cornil, Carnot) ; while the omentum itself grows to 
the adjacent wound-surfaces, and thus through changes in its structure 
completely closes up the defect. Yery often such an implantation of the 
omentum occurs spontaneously, as, for example, in the case of traumatic 
or ulcerative perforations of the intestine, stomach, gall-bladder, etc., 
and even large openings may be closed in this manner. As experimental 
investigations have shown, portions of intestine provided with blood- 
vessels may be implanted into other portions of the intestines, into the 
bladder (Enderle), stomach (Eeerink), and can heal perfectly in these 



306 



THE PROGRESSIVE CHANGES. 



locations with preservation of tlieir own epithelium. Likewise, portions 
of bone or eartilag'e connected with the periosteum or ])erieh()nclrium 
respectively, and with nutrient vessels, may be implanted into neighbor- 
ing tissue. 

Transplantations of tissues completely freed from their basement= 
structures have also been successfully performed, since cells loosened 
from tlieir connection with the organism are al)le to preserve tlieir vital- 
ity for a certain length of time. The cells of the epidermis are aV)le to 
live for the longest time; when kept cool they may be preserved alive 
for several (two to nine) days (AVeutselu-r claims to have been able to 
preserve ex)ithelium alive for twenty- two day> > . Ciliated epithelium may 
also be preserved alive for several days and still show mo\-ements of the 
cilia. Sj'ext to the surface-epithelium in this r(\s]^)ect stand the connec- 
tive tissues, while other tissues quickly die. the cells of the brain and 
kidney most rapidly, dying within a few hours after an obstruction to 
the blood-supply. According to the investigations which have l)een 
made up to the present time (Saltikow and others) the tissues of the 
skin, x^eriosteum, interarticular cartilages, muscle and cartilage easily 
preserve their vitality for two to three days. Morpurgo found cells of 
the periosteum to be capable of reiDroduction even after seven to eight 
days. The tissues of the A essels, tendons, and neurilemma appear to be 
somewhat more resistant. Exact statements with regard to this point 
cannot be made at present, sinee. on the one hand, the expiration of life 
does not take place suddenly, but gradually with the constant diminu- 
tion of vital ct'lls: and. on tlie other hand, the conditions under which 
the excised portions of tissue are preseiwed also influence the duration of 
life. 

Traiispltintaiions of skin give the best results, and were first recom- 
mended by Eeverdin and Thiersch for the healing over of broad, open 
wounds and have since been extensively ust'd for this purpose. The 
material used consists of pieces of skin which may be taken either from 
the same individual or from another person. Ordinarily, strips of skin 
removed by means of a sharp knife are used, which include the tips of 
the papilhie and the upi)er layers of the corium. Epithelium in conr.ec- 
tion with a thicker layer of the corium may also be snrce>sfully trans- 
planted, and in the case of injuries, large portions of the skin which have 
been completely torn oif may be again joined by healing to the deeper 
tissues on the very same spot from which they had been removed. 

The transplantation may be made either w^ton a fresh wound-surface 
or upon one already showing proliferation. The strips of skin are lield 
tirmly in i:)lace by means of moi>t bands of gauze. The pieces of skin 
become fastened to the surface of the wound by means of coagulated 
blood or lymph. In successful cases a firm union with the underlying- 
tissue takes ])lace within about eight days. 

The nourishment of the transplanted pieces (Fig. 176. (T) is olUained 
lirst from the tissue-fluids which exude from the underlying tissues. 
Later, there begins in the latter a vascular connective-tissue x^roliferation 
(h, c^, and the transplanted portion l^ecomes ])enetrated from below by 
new blood-vessels {g) accompanied by fll)ro]-)lasts. so that it finally be- 
comes interspersed with new blood-containing \ o-sels and areas of granu- 
lation tisstie. Under favorable conditions the old vessels may again 
become opened through the ingrowth of new a essels. 

The behavior of the trans])lanted portion varies in individual cases, 
the number of cells living and proliferating changing with the condi- 



TRANSPLANTATION OF SKIN. 30Y 

tions. Apart of the cells of the transplanted portion is always lost, and this 
is shown macroscopically in part by the repeated desquamation of the 
superficial layers of the epithelium (/). Other cells, both epithelial and 
connective-tissue cells, proliferate and produce new tissue. 

The final outcome of a successful transplantation is the covering over 
of the area with transplanted epithelium and in part also by transplanted 
corium. Through the latter it is made possible that the cicatricial area 
comes to possess papillae. To what extent in a given case the superficial 
layers of the cutis arise from the skin-graft or to what extent from the 
tissue upon which it is planted, cannot be determined. If the papillary 




Fig. 176.— Skin-graft four and one-half days old (formalin, haematoxylin, picrofuchsin) . a. Deep layer 
of the corium ; h, proliferating granulation-tissue ; c, boundary of proliferating zone ; d, e, transplanted 
portion of skin ; /. desquamation of the horny layer ; g, vascular offshoots and granulation-tissue extending 
into the transplanted connective tissue. X i07. 

bodies remain preserved, a portion of the tissue may be formed from 
immigrating fibroblasts. After a time the transplanted area comes to 
contain nerves which grow into it from the edges, and there is restored 
first the tactile sense (Stransky), later the sensibility of pain and temper- 
ature. Xew elastic tissue also develops, as in ordinary scars, from the 
ends of the old fibres. 

Besides skin-transplantations, there have been attempted transplanta- 
tions of almost all the tissues : periosteum, bone-marrow, bone, muscle, 
nerves, thyroid, pancreas, mammary gland, mucous glands, ovary, testis, 
etc. ; also of tissue-combinations, as, for examj^le, a rat's tail from which 
the skin has been stripped. Embryonal tissue has also been transplanted 



308 



THE PROGRESSIVE CHANGES. 



in a variety of ways. Finally the attempt has also been made to trans- 
plant tissues from one animal to another of a different species. 

Such transplantations have been made upon open wounds, into the 
subcutaneous tissues, peritoneal cavity, glandular organs and lungs, 
either by direct operative procedures or by the introduction of the tissue 
into the blood-stream through the blood-vessels. 

The results of all these experiments may be summed up as follows : 
In all transplanted tissues there occurs first a degeneration, and a jyavt of 
the tissue dies. After a certain time there usually results a proliferation 
of the remaining portion, which may lead to a new-formation of tissue. 
Connective -tissue cells form new connective tissue ; periosteum and bone- 
marrow form bone or connective tissue; muscle-cells, new muscle; carti- 
lage, new cartilage; surf ace epithelium, new epithelium (epithelial cysts). 
Of the glands the thyroid, mucous glands, and mammary glands may 
form new glandular tissue, while such a new-formation does not take 
place in the case of the kidney, liver, testis, and ovary. In the case of 
the liver only the epithelium of the bile-ducts proliferates. Only in the 
case of the transplantation of the ovary into the peritoneal cavity of the 
same animal can the ova rii)en and pregnancy occur (Knauer, Eibbert, 
Gregorieff). The tissues of young individuals in general show a greater 
capacity for proliferation than those of old people. In the case of the 
transplantation of complicated tissues, as, for example, the skinned tail 
of a rat, all the different tissues may produce new tissues and the whole 
piece grow. 

Embryonal tissue can likewise grow after transplantation and become 
differentiated, and it is shown that firm cartilage in particular, which in 
later life shows but little power of proliferation, is longer preserved and 
shows further growth, while the delicate soft tissue-formations easily die. 

After a certain time there occurs in almost all the transplanted tissues, 
as well as in the newly formed tissue, a retrograde change, and they are 
finally destroyed through the ingrowth of tissue from the neighborhood. The 
time at which this occurs varies with different tissues, and is dependent 
partly upon the character of the tissue, and partly upon the surrounding 
conditions. Implanted surface-epithelium can under certain conditions 
remain permanently, and give rise to epithelial cysts. Portions of thyroid, 
mammary gland, and pancreas are preserved for a long time. Cristiani 
found pieces of thyroid intact two years after implantation. The major- 
ity of the tissues, however, disappear within a few months. In glands 
which are not capable of proliferation the gland-cells die first. If all of 
the implanted piece is not destroyed it may become encapsulated. 

Tissue of different species, when transplanted, does not grow, but is 
either destroyed or encapsulated, sometimes quickly, sometimes slowly. 

According to the published observations, the implantation of tissue does 
not lead to the formation of a permanent tissue from the transplanted piece 
except in the case of the transplantation of skin. Il^evertheless, such an 
implantation may, under especial conditions, have a transitory or perma- 
nent value. The implantation of thyroid or pancreas tissue may for a 
certain time check the harmful consequences of the loss of these glands. 
Through implantation of a tissue into a defect a temporary filling of the 
latter may be produced, and the neighboring tissues are thus permitted to 
proliferate for a longer time, and to form a greater amount of new tissue 
along the framework afforded by the implanted portion, and so finally to 
close up the defect completely. Bone (not connected with nutrient ves- 
sels) when implanted into a portion of the skeleton is destroyed, and 



TRANSPLANTATION AND IMPLANTATION. 



309 



absorbed (equally so in either case, whether living bone or dead and 
macerated bone is implanted), and is replaced by new bone arising from 
the neighboring periosteum and bone-marrow. In this way there may 
be obtained a better healing of the bone-defect, and such implantations 
of bone or cartilage may also be made use of in the case of other tissues, 
for the stimulation of a more abundant production of tissue for the pur- 
pose of filling up tissue-defects. 

The transplantation of nerves has never resulted in the new-formation 
of a nerve from the transplanted piece. The attraction which the prod- 
ucts of disintegration of a nerve (Forssmann) exert upon the axis-cylin- 
ders growing into the wound may be utilized to direct the course of the 
growing nerves into certain channels. 

Literature. 

{Transplantation and Implantation.) 

Alessandri: Inuesti di tessuti viventi. Ref. Cbl. f. allg. Path., viii., 1897. 
Barth: Knochenimplantationen. Arch, f. kiln. Chir., 46 Bd., 1898; Beitr. v. Ziegler, 
xvii., 1895. 

Beresowsky : Transplant, v. Hautstiicken, aiif Thiere e. and. Species. Beitr. v. Zieg- 
ler, xii., 1892. 

Birch-Hirschfeld u. Garten: Verh. impl. embryonaler Gewebe. Beitr. v. Ziegler, 
xxvi., 1899. 

Bohm: Traumat. Epithelcysten. Virch. Arch., 144 Bd., 1896 (Lit.). 
Braun: Anheilimg imgestielter Hautlappen. Beitr. v. Bruns, xxv., 1899. 
Bruns, P.: Transplantation von Knochenmark. v. Langenbeck's Arch., xxvi., 1881. 
Busse: Fortleben losgetrennter Theile. Virch. Arch., 149 Bd., 1897. 
Cristiani: De la greffe thyreoidienne. Arch, de phys., vii., 1885; Jour, de phys., 
ii., 1901. 

Cohnheim u. Maas: Implantation v. Periost. in die Blutbahn. Virch. Arch., 70 Bd., 

1877. 

Djatschenko: Transplantation der Schleimhaute. Cbl. f. d. med. Wiss., 1890. 

Ehrhardt: Transplantation der Milz. Inaug.-Diss., Konigsberg, 1892. 

V. Eiselsberg: Einheilung der Katzenschilddrlise. Wien. klin. Woch., 1892. 

Enderlen: Einheilung v. Pfropfungen. Deut. Zeitsclir. f. Chir., 45 Bd., 1898; An- 
heilung getrockn. u. feuclit aufbewahrter Hautlappen. lb., 48 Bd., 1898; Trans- 
plant. V. Schilddriisen in die Bauchliohle. Mittheil. a. d. Grenzgeb.. iii., 1898; 
Reimplant. d. resec. Intermediarknorpels. Deut. Zeit. f. Chir., 51 Bd., 1899; 
Transplant, d. Netzes auf Blasendefecte. lb., 55 Bd., 1900; Deckung von Magen- 
defecten durch Netz. lb., 55 Bd., 1900. 

Fere: La famille teratoplastique (Implant, v. Blastoderm). Rev. de chir., 1895. 

Foa: Trapiant. delle ovarie. Riv. per le Sc. Biol., ii., 1900; La greft'e des ovaires. 
Arch. ital. de biol., xxxiv., 1900. 

Garre: Traumatische Epithelcysten. Beitr. v. Bruns, xi., 1894; Vorgange bei An- 
heilung d. Thiersch'schen Transplant. Beitr. v. Bruns, iv., 1889. 

Goldmann: Die klinstliche Ueberhautung offener Krebse durch Hauttransplantation, 
Cbl. f. allg. Path., i., 1890; Schicksal der verpflanzten Hautstlicke. Beitr. v. 
Bruns, xi., 1894. 

Goldzieher: Implantationen in die vordere Augenkammer, Arch. f. exp. Path., ii., 
1874. 

Grawitz: Widerstandsfahigkeit leb. Gewebe. Deut. med. Woch., 1891. 
Gregorieff: Schwangerschaft bei Transpl. v. Ovarien. Arch, f. Gyn., 22 Bd., 1897. 
Grohe: Vita propria d. Zellen d. Periosts. Virch. Arch., 155 Bd., 1899. 
Hedon: Greffe souscutanee du pancreas. Arch, de phys., 1892, 

Henle u. Wagner: Transplant, ungestielter Hautlappen. Beitr, v. Bruns, 24 Bd., 
1899. 

Herlitzka: Transplant, des testicules. Arch. ital. de biol., xxxii., 1899; Ovarien- 
transplant. Biol. Cbl., xx., 1900; Arch. ital. de biol., xxxiv., 1900. 

Joachimsthal : Sehnentransplant. Eulenburg's Jahrb., viii., 1898 (Lit.). 

Jungengel: Die Hauttransplantation. Verh. d. Phys.- med. Ges. zu Wiirzburg, 25 
Bd., 1891. 

Karg: Studien iiber transplantirte Haut. Arch, f. Anat. u. Phj^s., 1888. 
18 



310 



THE PROGRESSIVE CHANGES. 



Kaufmann: Enkatarrhapliie v. Epitliel. Virch. Arch., 97 Bd., 1884. 
Knauer: Ovarientransplantation. Cbl. f. Gyn., 1896; Vv ien. klin. Woch., 1899. 
Laurent: Rech. sur la greffe osseuse, Bruxelles, 1893. 
Leopold: Transplant, v. Knorpel. Virch. Arch., 85 Bd., 1881. 

Ljungren: Lebensdauer d. Hautepithels ausserh. d. Organismus. Deut. Zeit. f. Chir., 
47 Bd., 1898. 

Leob: Trauspl. v. weiss. Haiit auf Defecte in scliwarzer u. umgek. Arch. f. 

Entwickluugsmech., vi., 1898. 
Lubarsch: Zur. Lehre v. d. Geschwillsten ii. Infectionskrankh., Wiesbaden, 1899. 
Marchaiid: Knochentransplantation. Verh. d. Deut. path. Ges., ii., Berhn, 1900. 
V. Mang-oldt: Ueberliautung von Wunden durch Epithelaussaat. Deut. med. Woch., 

1895; Einpflanz. v. Rippenknorpel in Kehlkopf. Langenbeck's Arch., 50 Bd., 1899. 
Minkowski: Unters. liber Diabetes mellitus. Arch. f. exp. Path., 31 Bd., 1893. 
Morpurg-o: Vita propria d, Periostzellen. Virch. Arch., 157 Bd., 1899. 
Mosse: La greffe osseuse heteroplast. Arch, dephys., viii., 1896. 
Neumann: Nierentransplantation. Arch. f. Entwickelungsmechan., vi., 1898. 
Ollivier: Traite exper. et clin. de la regenerat. des os, 1867; De la greffe osseuse chez 

I'homme. Arch, de phys., 1889. 
Pascale: Innesti ossei. XII. Congr. Chir., Roma, 1897. 

Plessing: Hautverpflanzung nach Thierscli. Langenbeck's Arch., 37 Bd., 1888. 
Raehlmann: Anheilung transplant. Lippenschleimhaut. Beitr. v. Ziegler, xxvi., 
1899. 

Reerink: Experimente liber Transplantationen am Magen. Beitr. v. Ziegler, xxviii., 
1900. 

Reverdin: De la greffe epidermique, Paris, 1872 (u. Gaz, des hop., 1870, 1891); 
Transpl. de peau de grenouille sur des plaies humaines. Arch, de med. exp., iv., 
1892. 

Ribbert: Das patholog. Wachsthum d. Gewebe, Bonn, 1896; Verand. transplant. 
Gewebe. Arch. f. Entwickelungsmech., vi. ; Transplant, v. Ovarium, Hoden, 
Mamma. lb., vii., 1898; Exp. Erzeugung von Epithel- u. Dermoidcysten. Deut. 
Zeit. f. Chir., 47 Bd., 1898. 

Rutkowski: Harnblasenplastik. Cbl. f. Chir., 1899. 

Saltykow: Transpl. zusammenges. Theile. Arch. f. Entwickelungsmech., ix., 1900. 
Scbeff: Die Replantation der Zahne, Wien, 1890. 

Schloifer; Osteoplastik bei Defecten d. Tibia. Beitr. v. Bruns, xxv., 1899. 
Schiiller: Sclialenhaut des Iliilinereies. Monatssch f. Unfallheilk., 1899. 
Schultz: Transpl. v. Ovarien auf mannl. Thiere. Cbl. f. allgem. Path., xi., 1900. 
Stransky: Sensibilitat transpl. Hautstiicke. Wien. med. Woch., 1899. 
Sultan: Transpl. v. Schilddriisen. Cbl. f. allgem. Path., 1898. 
Schweninger: Ueber Transplant, u. Implant, v. Haaren, Munclien, 1875. 
Tietze: lietzplastik. Beitr. v. Bruns, xxv., 1899. 

Valan: Sull' innesto dell' osso sul cranio. Arch, per le Sc. Md., xxii., 1898; Arch, 
it. de bioL, xxxi. 

"Weiss: Transplant, v. Bindehaut auf Hornhaut. Arch. f. Augenh., 33 Bd., 1896 
Wentscher: Eigenleben menschl. Epidermiszellen. Beitr. v. Ziegler, xxiv., 1898, 
Wetzel: Transplantationsversuche mit Hydra. Arch. 1 mikr. Anat., lii., 1897. 
Zahn: Sur le sort des tissus implantes dans I'organisme. Congres med. Internal, de 

Geneve, 1876; Schicksal in den Organismus implant. Gewebe. Virch. Arch., 95 

Bd., 1884. 

IV. The Metaplasia of Tissues. 

g 89. Metaplasia of a tissue is that process by which au already fully - 
developed tissue is changed into another tissue without passing through an 
intermediate cellular stage — that is, through the stage of an embryonic 
or formative tissue. Such a transformation occurs only in tissues which 
are closely related to each other, particularly in the connective tissues. 
All the tissues belonging to this group may, under pathological condi- 
tions, be transformed, one into another, without the occurrence of any 
intermediate proliferation — a phenomenon which in itself is not surpris- 
ing, as such transformations occur also under normal conditions. Mu- 
cous tissue becomes changed to adipose tissue through the conversion of 
the stellate connective-tissue cells into round fat-cells through the tak- 
ing-up of fat, while the mucous ground -substance disappears. Lymph- 



METAPLASIA 



311 



adenoid tissue after the disappearance of the lymphoid elements may be 
converted into adipose tissue throngh the taking-up of fat into the cells 
of the reticulum. 

Through disappearance of the fat, adipose tissue acquires the appear- 
ance of mucous tissue, and at times may also contain mucin. If the 
ground-substance of hyaline cartilage becomes liquefied to form a mucin- 
containing jelly, or if it becomes completely dissolved, the cartilage -cells 
thus set free (Fig. 177, a) become changed to stellate cells anastomosing 
with one another (c, Z>), so that a tissue is formed which corresponds in 
its structure to mucoid tissue or to the reticulum of the bone-marrow. 
Through the taking up of fat this tissue may become changed into adi- 
pose tissue ; through the collection of round cells in its meshes it beconaes 
a cellular marrow-tissue. If the basement-substance of hyaline cartilage 
becomes fibrous, and changes at the same time into a glue -producing sub- 




FiG. 177.— Metaplasia of cartilage into reticular tissue, in arthritis fungosa (alcohol, haematoxvlin) 
a. Hyaline cartilage ; &, tissue consisting of branched cells ; c, cartilage-cells, set free by the liquefaction of 
the basement-substance of the cartilage, and becoming transformed into cells of mucous tissue. X 400. 

stance, there is formed a fibro-cartilage. If the cartilage -cells lose their 
characteristic nature and become changed to flat connective-tissue cells, 
the cartilage becomes changed into ordinary connective tissue. 

When portions of cartilage change into marrow tissue (Fig. 178, a, 
k, i), other portions of the same may become converted into osteoid tis- 
sue (/) and bone, whereby the ground-substance is changed into a 
glue-producing substance and impregnated with lirne-salts, vfhile the 
cartilage -cells become bone -cells, in the neighborhood of which the 
basement-substance of the bone forms the serrated bone-corpuscles. If 
connective tissue becomes directly changed into bone (Fig. 179) there 
occurs in the first place a thickening of the ground- substance (&), and 
later a deposit of lime-salts (c), whereby the connective-tissue cells (d) 
come to lie in serrated spaces and are changed to bone-cells {d^). 

In the transformation of connective tissue into mucous tissue, the 
fibrillse disappear, and there appears in their place a gelatinous mucus. 
Should numerous lymphoid round-cells collect in a fibrillar connective 
tissue, and if at the same time there occurs a loosening or disappearance 
of the connective-tissue fibres while the connective- tissue cells persist 



812 



THE PROGRESSIVE CHANGES. 



and unite, through the formation of processes, to form a reticular tissue, 
there may be developed a lymphadenoid tissue. 

The metaplasia of connective tissue is to be distinguished both from 
simple degeneration and also from processes of growth. From the 




c c 3 € 



riG, 178.— Formatiou of bone from cartilage, in a callus fourteen days old (Miiller's fluid, picric acid, 
haematoxylin, carmine), a, Hyaline cartilage; Ik marrow-spaces: c, blood-vessel; (?, cellular, c, flbrocel- 
lular JmaiTow ; f, osteoid tissue ; g, osteoblasts ; cartilage-cells freed through the disappearance of the 
ground-substance: /, proliferating cartilage-cells in opened capsule; A', proliferating cartilage-cells in 
closed capsule. X 200. 

former no ne\Y tissue arises, but the old one dies; in the latter there 
arises through cell -division a new tissue rich in cells. Metaplasia 
stands, in a certain sense, midway between these processes. It gives 
rise to a new tissue, but cell-proliferation is either wholly absent or 
plays but a small part. 

In many ways the process is allied to the retrograde changes ; thus, 
for example, the metaplasia into mucous tissue is a process closelj^ re- 
lated to mucous degeneration. The newly formed tissue, moreover, is 
not infrequently transitory. On the other hand, proliferation-processes 

are very frequently seen following 
metaplasia, thus showing another re- 
lationship to the progressive disturb- 
ances of nutrition. Further, such 
metaplastic processes occur frequent- 
ly in association with proliferation, 
especially the new - formation of 
bone, since in this case an already 
characteristic, developed tissue (Fig. 
178) passes over into another tissue. 

Metaplasia of epitlieJium occurs 
most frequently in mucous mem- 
branes showing chronic inflamma- 
tory processes, as, for example, in 
the mucosa of uterus, urethra (gon- 




FiG. 179.— Formation of bone from connective 
tissue (alcohol, ha?matoxylin). Cross-section 
through a bone trabecula in process of formation ; 
from an ossifying fibroma of the periosteum of 
the upper jaw. a. Connective tissue ; h, thick- 
ened tissue, forming the groundwork of the new 
bone ; c, deposits of lime-salts ; d, connective-tis- 
sue cells ; di, bone-cells. X ISO. 



METAPLASIA. 



313 



orrlioea), nose (ozgena), and of the trachea, whereby the cylindrical epithe- 
lium becomes changed into flattened. 

This transformation takes place through a change in the character of 
the regenerating epithelium as the result of repeated loss of the original 
epithelium. In the stratified squamous epithelium of a mucous mem- 
brane there may occur also a cornijication of the uppermost layers of cells, 
both in regions where squamous epithelium is normally present, and also 
in regions which normally possess none, as, for example, in the ureters, 
as well as in places where it has been formed pathologically, as in the 
nose and uterus. 

Literature. 

{Metaplasia. ) 

Finger: Die chronisclie Uretliralblennorrlioe. Arch. f. Derm., Erganzungsheft, 1891. 
Hansemann: Studien lib. Specificitat, Altruismus u. Anaplasie d. Zellen, Berlin, 1893. 
Hildebrandt: Ueber einen Katarrli d. weibl. Geschlechtsorgane. Samml. klin. 
Vortr., No. 32. 

Kanthack: Stud. lib. d. Histologie d. Larynxschleimhaut. Virch. Arcli., 119 and 120 
Bd., 1890. 

Klistner: Plattenepithel auf Uteruspolypen. Cbl. f. Gyn., 1884. 

Liebenow; Ueber ausgedehnte Epidermisbildung der Harnwege. Inaiig.-Diss., Mar- 
burg, 1891. 

Neelsen: Histol. Verand. i. d. cliron. entziindet. Urethra. Viertel jahrsschr. f. Derm., 
1887. 

OMoif: Epitlielmetaplasie u. Krebsbildung in Gallenblase u. Trachea. Inaug. Diss., 
Greifswald, 1891. 

Sangalli: Die Metaplasie d. krankh. Gewebe. Int. Beitr., Festschr. f. Virchow, ii., 
Berlin, 1891. 

Schmiedeberg : Die chemische Zusammensetzung des Knorpels. Arch. f. exp. Path., 
1891. 

Schuchardt: Ueber d. Wesen d. Ozaena. Samml. klin. Vortr., No. 340, Leipzisr, 
1891. 

Virchow: Gesammelte Abhandl., Frankfurt, 1856, pp. 500, 509; Cellularpathol , iv. 

Aufl., p. 70. Virch. Arch., 8 and 97 Bd. ; Deut. med. Woch., 1884. 
Zeller: Plattenepithel im Uterus. Zeitschr. f. Geburtsh., i., 1885. 



CHAPTER VII. 



Inflammation. 

I. The Early Stages of Acute Inflammation. 

§ 90. Under the designation inflammation are groni)ed those patho- 
logical phenomena which represent a combination of different patholog- 
ical processes, consisting on the one hand of tissue=degenerations and 
tissue=proliferations, and on the other of pathological exudations from 
the blood=vessels. Degenerations of tissue and })athoJogical exudations init- 
iate the process ; ivith these tissue-proliferation is sooner or later associated, 
the latter leading in the further course of the process to a compensation 
for the disturbance — that is, to healing. The proliferation of tissue may, 
therefore, be regarded as regenerative, but such new-formation of tissue 
may be in excess of that which is useful to the body. The tissue-degen- 
erations and proliferative processes described in the previous chapters 
appear for the greater part as participating factors in inflammation ; the 
process acquiring its inflammatory character through the combination of tissue- 
degenerations and tissue-proliferations icith pathological exudations. 

Deeper tissue -lesions — that is, injury of tissues containing blood-vessels — 
which in some way or other affect the vascular system, will, therefore, 
constantly bear at some time during their course the character of an inflamma- 
tion. The formation of scar tissue, the healing of transplanted tissues, as 
briefly described in the last chapter, always ta'ke place through processes 
essentially inflammatory in nature. 

Exudation in acute inflammation is constantly associated with a 
pronounced hypercemia, which api^ears even before the beginning of the 
exudation, and hence ushers in the latter. As a result of the combina- 
tion of hypersemia and exudation the inflamed tissue becomes reddened 
and swollen. When situated on the surface of the body, where a cooling 
of the tissues takes place, the increased flow of warm blood from the 
deeper tissues causes a local increase of temperature. If the tissue af- 
fected contains sensory nerves, the sensation of pain will be produced as 
the result of the changed conditions in the inflamed area. 

Redness, swelling, increased warmth, and painfulness of the in- 
flamed tissue are phenomena which even in ancient times were regarded 
by physicians as the signs of inflammation ; and rubor, tumor, calor, and 
dolor were designated by Celsus, at the beginning of our era, as the 
cardinal symptoms of inflammation. To these four was then added 
still a further symptom, functio Isesa, altered function of the inflamed 
tissue. 

The causes of inflammation may lie either in mechanical, thermal, 
electrical, or chemical influences, as well as in the influence of parasites. 
The common characteristic of all these injurious agencies is the produc- 
tion^ in the first place, of a local tissue-degeneration, which, when of a certain 
extent and intensity, is associated with disturbances of the circidation and of 
the vascidar secretion. The causes of inflammation are not specific; any 

314 



THE EARLY STAGES OF ACUTE INFLAMMATION. 



315 



injurious agent may excite inflammation if on the one hand its action is 
sufficiently intense to cause certain disturbances of circulation in asso- 
ciation with tissue-degenerations, but on the other hand not so intense as 
completely to destroy the tissue and stop the circulation. 

The great majority of the causes of inflammation reach the human 
organism from the outside, but excitants of inflammation may be formed 
also within the body. In the first place bacteria which have penetrated 
into the tissues very often form within their protoplasm or from sub- 
stances present in the body certain products which are callable of excit- 
ing inflammation. Moreover, substances that excite inflammation may 
arise within the organism without the aid of parasites ; particularly as 
the result of the death of large masses of tissue from any cause, as, for 
example, as the result of anaemia, or when as the result of disturbances 
of metabolic processes (gout) products of metabolism are deposited in 
the tissues. 

The causes of inflammation may act upon the tissues either from the 
portions of the body accessible from without, or from the lymi)h and the 
blood; and we may, therefore, distinguish ectogenous, lymphogenous, 
and hsematogenous inflammations. Through the spread of an inflam- 
mation to neighboring tissues there arises an inflammation by con= 
tinuity ; as the result of the transportation through the lymph or blood 
stream of an agent causing inflammation, there are produced metastatic 
inflammations. If injurious substances are discharged through the 
excretory organs, excretory inflammations may arise. 

When a local injury to tissues has reached such a degree as to pro- 
duce the exudation characteristic of an inflammation, there is usually 
found in the first place a congestive hypersemia, as a result of which 
the blood flows through the dilated blood- channels with increased veloc- 
ity. After a short time there is a lessening of the speed of the circula- 
tion which leads finally to an abnormal slowing of the bIood=current. 

The first disturbances of circulation, which find expression in the 
congestive hyperaemia, may be due either to a stimulation or paralysis 
of the vasomotor system or to a direct action upon the vessel-walls, par- 
ticularly upon the arterial walls, leading to a dilatation of the lumen. 
Although these disturbances very frequently precede the inflammatory 
exudation, th^y do not form an essential characteristic of inflammation, 
and occur very often without being followed by an inflammatory exuda- 
tion. Further, they may be absent during the course of an inflammation. 
The circulatory disturbances characteristic of inflammation are shown 
only when the^slowing of the blood=current and the pathological 
exudation from the blood=vessels set in. The slowing of the blood- 
stream in the dilated channels and the pathological exudation are de- 
pendentSiiDonJa change in structure, an alteration of the vascular walls, 
through which there results a lasting dilatation of the vessel and an 
adhesion of pie blood to the vessel-wall, causing an increase of friction- 
resistance aua an increased permeability of the vessel -wall. In the capil- 
laries the persistent dilatation is in great part the result of relaxation of the 
connective tissue surrounding the capillaries, inasmuch as the thinness of the 
capillary walls makes this tissue bear the greater part of the blood-press- 
ure resting upon them. 

The tissue=Iesion which leads to the phenomena of inflammatory dis- 
turbances of circulation and exudation usually affects all parts of the 
tissue, but under certain conditions may be limited to the vessel-wall, 
particularly in the case of a hiematogenous inflammation, in which the 



316 



INFLAMMATION. 



injurious agent acts from the blood. However, the tissue in the region 
adjoining the capillary walls must soon become involved in association. 
The tissue-changes brought about by the excitants of inflammation are 
sometimes only slight, and even on microscopical examination are either 
not recognizable at all or only with difificulty ; at other times they are 
more severe, so that they may be easily recognized even on macroscopic 
examination. The latter is particularly the case when some time has 
elapsed after the action of the injurious agent. During the further 
course of the inflammatory process there are often added to the lesions 
produced directly by the causes of inflammation other tissue-changes, 
which are brought about by the inflammatory disturbances of circulation 
and the collection of exudate in the tissues. 

If in any tissue the cause of inflammation has led to that alteration 
of the vessels which is the requisite antecedent of an inflammatory dis- 
turbance of the secretion of the vessels, i. e. , the formation of an inflam- 
matory exudate, and if as a result of this there is already evident a 
slowing of the blood-stream, the capillary circulation becomes irregular, 
and there occurs here and there either stagnation or a permanent or 
transitory stasis. Since in this event the white blood -corpuscles often 
remain clinging to the vessel-walls while the red blood-cells are carried 
on, there arises in the capillaries a more or less marked increase of 
white blood=corpuscles as compared to the red. In the veins, in which 
there can be distinguished in the normal circulation an axial red stream 
and a peripheral plasma-zone free from cells, a greater or less number of 
leucocytes pass over into the peripheral plasnia=zone, when the slow- 
ing of the circulation has reached a certain degree. A still greater slow- 
ing of the current leads to the passing over of blood-plates and red 
blood-cells into the peripheral plasma-zone, and finally the difference 
between the axial-stream and the peripheral zone maybe entirely lost. 

When leucocytes pass over into the peripheral zone they either roll 
along in the same or cling to the wall of the vein, either to roll on again 
after a time or to remain- permanently attached. If this occurrence leads 
to a marked accumulation of leucocytes along the vein-walls, the condi- 
tion is known as the marginal disposition of the white corpuscles (Fig. 
180, d). 

Following the accumulation of the leucocytes in the capillaries and 
the marginal disposition in the veins there occurs later an emigration of 
the leucocytes (Fig. 180, d, e) from the vessels involved, and at the same 
time ^pouring-out of fluid from the vessels into the tissues. 

The emigration of the white corpuscles is an active process, which 
is accomplished through the amoeboid movement of the cells, and to a 
certain extent occurs under normal conditions. The cause of the marked 
emigration seen in inflammations is doubtless a change in the vessel - 
walls, which favors the clinging of the cells to the walls and their pas- 
sage through the latter. According to investigations by Arnold, Thoma, 
and others, the leucoc!|'tes pass out through the lines of c^nent-substance 
between the endothelial cells ; and in the alteration of the vessel -wall due 
to inflammation localized defects occur in the wall as the result of the 
widening of these lines. The emigration is accomplished by the leuco- 
cytes first sending a process through the vessel -wall, the rem^ainder of 
the cell-body then flowing after the process, until finally the entire cell- 
body is outside of the vessel. Arrived here the leucocytes first remain 
lying in the immediate neighborhood of the point of diapedesis, but 
often wander farther, the direction of the wandering being determined 



INFLAMMATORY EXUDATION. 



317 



partly by mechanical stimuli, partly by chemotaxis—t\idit is, the repelling 
or attracting influences exerted by chemical substances present in solu- 
tion in the tissue- juices. PossilDly cheniotactic influences sometimes 
exert an action even upon the leucocytes in the capillaries or those in 
the peripheral zone of the veins. The leucocytes emigrating from the 
vessels are chiefly polynuclear forms, which constitute about seventy per 
cent, of the white blood- corpuscles in the blood. The number of the 
migrating cells is sometimes large, sometimes small. 

The pouring=out of the fluid exudate, whose composition always 
differs more or less from that of the normal tissue -lymph, and which is 
characterized by a relatively high albumin- content, is a process which is 




Fig. 180.— Inflamed buman mesentery (osmie-acid preparation), a. Normal trabecula; Z), normal 
epithelium (endothelium); c, small artery ; cZ, vein with leucocytes arranged peripherally : e, white blood- 
cells, which have emigrated or are emigrating ; /, desquamating endothelium ; /j, multinuclear cells ; g, 
extravasated red blood-cells. X 180. 

also to be referred to an alteration of the vessel-wall, in consequence of 
which the secretory function of the latter suffers a disturbance. It takes 
place at the same time with the emigration of the leucocytes, but may 
begin before this event, and may occur also in cases in which the emigra- 
tion of the leucocytes does not take place at all, or remains within very 
narrow limits. The composition of the exudate is dependent, in all cases, 
partly upon the especial property of the affected vessels, which always 
varies according to the tissue -formation to which the vessels belong, and 
partly upon the degree of vascular alteration ; and it may be assumed 
that the albumin -content is the higher the greater the damage to the 
vessel -walls. If the extravasated fluid contains fibrin ogenic substances 
and fibrin-ferment, and if, on the other hand, no influences opposed to 
such a change are acting, coagulation — that is, a separation of fibrin 
— takes place. 

If the alteration of the vessels is of a very high degree, or if at the 
same time there is a marked stasis, red blood =cel Is may also pass out of 
the vessels (Fig. 180, g) along with the fluid, either by rhexis or dia- 



318 



INFLAMMATION. 



pedesis. According to Thoma aud Engelmann the diapedesis occurs 
particularly in those places where Ibucocytes have previously passed 
through the vessel-wall, aud the escape of red blood-cells may follow 
very quickly by the same route. Since the red blood-cells are not mo- 
tile, their escape must be regarded as a passive process performed under 
the influence of the pressure within the capillaries. 

The escape of blood^plates into the exudate may take place both iu 
exudates rich iu cells and those containing but few, but occurs iDarticu- 
larly in exudates characterized by a rich content in fibriu and red blood- 
cells. 

Tissue=proliferation — that is, the di^^sionof cells and nuclei — is first 
recognizable about eight hours after the action of the injurious agent; 
and in many cases appears much later. There are present, therefore, in 
case the inflammation does not arise in a tissue already in a state of pro- 
liferation, the characteristic appearances of inflammatory exudation, and 
with it also the tissue-degeneration, long before the proliferation begins. 

The clinical significance of tlie term inflammation {inflammaUo, iMogosis) has 
changed but little in the course of time, since the cardinal sj'mptoms of inflammation 
set forth by Celsus, and ajccepted by Galen, are recognized as such at the present day. 
Nevertheless, the views regarding the difLcrentiation of the essential from the unessential 
in the^ sj^mptom-complex of inflammation and the accurate determination of the true 
nature of the process have differed greatly. A comparison of the expressions concerning 
these points made by the more modern writers {TircJiow, xon liecklinghausen, Cohnheim, 
Poiifick, Samuel, Thoma, Neumann, Strieker, Heitzmann, Graiciiz, Leber, Metsc?inikoff, 
and others) shows that no single writer defines inflammation in the same w^ay as any 
other, or interprets in exactlj^ the same way any one of the individual phenomena of 
inflammation. Ponfick designates as the cause of inflammation the disturbance of equi- 
librium in the tissues, " but hesitates to designate retrogressive changes as an indis- 
pensable attribute of the inflammatory process, and doubts wholly that they should be 
regarded as the point of departure and the chief feature of the process." I am of the 
opinion that "a disturbance of the tissue-equilibrium" is nothing more than a degener- 
ative change of tissue, and regard Ponfick' s statement, though directed against my defi- 
nition, as harmonizing with ui}^ views. Moreover, I once again emphasize the fact 
that the alteration of the vessels is a necessary requisite for exudation, and that this 
alteration is nothing else than a tissue-degeneration. 

It was formerly believed that hypercemia was the essential symptom of inflamma- 
tion. Rokitansky held that every inflammation was characterized by a dilatation of the 
capillaries, slowing of the blood-stream, and by stasis, which was caused by a thicken- 
ing of the blood through the effusion of serum and the adhesion of the red blood-cells 
to one another. Henle, Stilling, and Bokitansky attributed the dilatation of the vessels 
and the slowing of the circulation to a parah'sis of the nerves of the vessels, the cause 
of which, according to Renle and Rokitansky, is an increased stimulation of the sensory 
nerves; while according to Stilling, the cause lies in a paralysis of the nerves due to 
the inflammatory irritant. Eisenmann, Heine, and Briicke sought to attribute the cir- 
culatory disturbances to a primary spasm of the vessels brought about by the irritation 
of sensory nerves, which produces behind the contracted portions of the vessels a slow- 
ing of the current, irregular circulation, and finally also stasis. Yogel, Emmert, Paget, 
and others, on the other hand, attributed the dilatation of the vessels and the stasis to 
an abnormal attraction of the blood by the tissues. Against these views it must be 
maintained that all the disturbances of circulation produced by contraction or dilatation 
of the vessels, indeed, introduce or accompany the inflammatory disturbances of circu- 
lation, i.e., those leading to exudation, and may exert a modifying influence upon the 
course of the inflammation, but do not form an essential part of the process, and may 
be entirely wanting, or may appear without the accompaniment of an inflammatory 
exudate. 

Rokitansky sought to explain the pouring out of fluid from the vessels in inflamma- 
tion by the assumption that with the dilatation of the vessels the walls of the latter be- 
came thinned and more permeable. Vogel, C. Emmert, and Paget, on the other hand, 
made this phenomenon also dependent upon an increased attraction between the blood 
and the tissue parench^^ma or juices. Virclioir, however (1854), believed that part of the 
exudate, and indeed that which collected in the tissue-spaces and is poured out upon 
the free surfaces of the body, to be tlie result of mechanical pressure in the vessels, i.e., 



THEORIES OF INFLAMMATION. 



319 



pressed-out blood-serum; while a part, which is chiefly taken up by the "irritated" 
cells, is to be regarded as a product of an increased drawing of the blood-elements 
through the tissues, as a kind of nutritive educt. Of the cells collecting in the in- 
flamed area, he believed that all originate from a proliferation of the tissue-cells oc- 
curring as the result of the action of the inflammatory irritant. 

The recognition that the formation of the exudate is to be referred to an injury of 
the vessel-walls we owe chiefly to Gohnheim, whose investigations along various lines 
were completed by Samuel, Arnold, Tlioma, Binz, and others. CoJinheim also showed 
that in inflammation the colorless corpuscles emigrate, and form an essential constituent 
of the inflammatory exudate. 

Butrochet (" Recli. anatomiques et physiologiques sur la structure interne des ani- 
maux et des vegetaux et sur leur motilite," Paris, 1842, p. 214) and Waller {Philosoph. 
Magaz., xxix., 1846, pp. 271, 398) had as early as the years 1842 and 1846 already de- 
scribed the escape of colorless corpuscles from the blood-vessels. These observations 
had, however, fallen completely into oblivion until GoTinheim, in 1867, rediscovered the 
phenomenon. 

According to researches of ScTiMarewsky {Pfliiger's Arch., Bd. i.), the peripheral dis- 
position of the leucocytes in the veins is purely a physical phenomenon. If fluids, in 
which are suspended finely powdered substances of different specific gravity, are made 
to flow through tubes, it will be found that at a certain degree of retardation of the 
current, the bodies of lighter specific gravity pass over into the peripheral zone, and at 
a more marked retardation the heavier bodies also enter this zone. 

For the occurrence of the emigration of the white corpuscles, it is necessary, 
according to the researches of Binz, TJioma, and Lavdoicsky, that they be capable of 
motion and of adhering to the vessel-wall. According to these observers, the emigra- 
tion of the white blood-cells is not a purely passive, but is in part at least an active 
process. If the amoeboid power of the white cells be lessened by means of irrigation 
of the mesentery with a 1.5-per-cent. solution of salt (Thoma), or if the vital energy 
of these ceils be lowered by means of quinine or iodoform (Binz, Appert, Kerner), 
there results an inhibition of emigration. On the other hand, Pekelharing believes 
that quinine, oil of eucalyptus, and salicylic acid cause a contraction of the veins, 
lessen the permeability of their w^alls, and thereby hinder the passing-out of the white 
cells. This view is rejected, however, by Bisselhorst, who observed a dilatation of 
the veins after irrigation of the tissues with quinine, carbolic acid, salicylic acid, and 
mercuric chloride. As there occurs in this case a retardation of the current after a 
transitory acceleration, without an emigration of the leucocytes collected in the periph- 
eral zone ; and as, on the other hand, leucocytes from blood-vessels that have been irri- 
gated for an hour with quinine still retain complete vitality {Eberth), BisseUwrst is of the 
opinion that the drugs mentioned so change the inflamed vesscl-w^all that an adhesion of 
the leucocytes rolling along the wall either cannot occur at all or only with difficulty. 

It is very probable that a lesion of the vessel-wall is not absolutely necessarj^ for 
the emigration of leucocytes ( Tlioma). Since vasomotor disturbances of the circulation 
can produce migration {mn Recklinghausen, Thoma), it is probable that all of the con- 
ditions necessary for this process are furnished by a slowing of the blood-stream with 
peripheral disposition of the colorless corpuscles and the ability of the leucocytes to 
perform amoeboid movements and to adhere to the vessel-walls. It is possible that 
differences in the water-content of the tissues {Thoma) also exert some influence, since 
an increased amount of water causes increased amoeboid movement. It is also possible 
that the presence, in the tissue-fluids, of substances having active chemotactic proper- 
ties may cause emigration of those leucocytes in the peripheral zone which are adherent 
to the vessel-wall. 

According to the investigations of Arnold, Thoma, and Engelmann, there is present 
between the edges of the endothelial cells a soft cement-substance which suffers a change 
in the circulatory disturbance associated with cell-migration. This change may some- 
times, but not always {Lowit), be recognized, on' histological examination, in the form 
of numerous circumscribed widenings of these intercellular areas {Engelmann). If leu- 
cocytes pass through these places in great numbers the cement-substance becomes still 
more permeable, and may then permit red cells also to pass through in rapid succession 
{Thoma^. 

Wandering cells are found normally in many tissues {wn Recklinghausen), and 
wander from these partly into the lymph-vessels {Bering, Thoma), and under certain 
conditions also into the blood-vessels {Bubnoff, Schulin, Ranvier, Senftleben), or onto the 
surface of the mucous membranes, where they penetrate between the epithelial cells. 
They are found constantly in large numbers about the nodes of lymphadenoid tissue 
in the mucous membranes, and wander from these through the epithelium onto the^ 
surface. According to observations by Kunkel and Siebel, small number* also reach the' 
free surface of the alveoli of the lungs. 



320 



INFLAMMATION. 



The inflammatory disturbances of circulation and the formation of exudates may 
be most easily folloAved in the transparent membranes of cold-blooded animals, particu- 
larly in the mesentery, or the extended tongue or the spread-out web of the frog. In 
the frog's mesentery, which has been spread out on a suitable glass plate, circulatory 
disturbances and inflammation develop simply through exposure to the air and the 
resulting evaporation; in the case of the tongue and web, it is necessary to cauterize in 
order to produce an inflammation. By the employment of suitable apparatus the cir- 
culation of the blood and the formation of the inflammatory exudate ma.y also be ob- 
served under the microscope in the thin membranes of mammals (mesentery of rabbit, 
wing-membrane of bat), and observations thus made harmonize wholly with those made 
upon the frog. 

Literature. 

{Inflammation.) 

Aufrecht: Ueber Entzlindung, Pathol. Mittheilungen, i., Magdeburg, 1881. 
Brault: Etude sur I'inflammation, Paris, 1888. 

Cohnlieim: Ueber Entziindung und Eiterung. Virch. Arch., 40 Bd., 1876; jSTeue 
Untersuchungen liber Entziindung, Berlin, 1878; Noch einmal die Keratitis. 
Virch. Arch., 61 Bd., 1874; Vorles. liber allg. Pathologic, Leipzig, 1882. 

Cornil et Ranvier: Man. d'histol. patholog., i., Paris, 1901. 

Councilman: Inflammation. Ref. flandb. of Med. Sciences, 2ded., 1902. 

Franke: Die menschliche Zelle, Leipzig, 1891. 

Grawitz: Atlas der patliol. Gewebelehre, Berlin, 1893. 

Hektoen: Old and Modern Theories of Inflammation. Phil. Med. Jour., 1898. 

Henle: Handb. d. ration. Pathologic, Braunschweig, 1844. 

Janowski: Die Ursachen der Eiterung. Beitr. v. Ziegler, xv., 1894. 

Landerer: Zur Lehre von der Entziindung. Volkmann's Samml. kl. Vortr., No. 259, 

1885 ; Die Gewebsspannung, Leipzig, 1884. 
Leber: Die Entstehung der Entziindung, Leipzig, 1891. 
Letulle: L 'Inflammation, Paris, 1893. 

Lowit: Entstehung des Lungenodems. Beitr. v. Ziegler, xiv., 1894. 
Lubarsch: Entziindung. Ergebn. d. allg. Path., iii., 1897; Deut. med. Wocli., 1898. 
Metschnikoff : Leg. sur la pathologic comparee de I'inflammation, Paris, 1892. 
Neumann: Ueber den Entzlindungsbegriff. Beitr. v. Ziegler, v., 1889. 
Ponfick: Die Entwickelung der Entzlindungslehre im. 19. Jahr. Berl. klin. Woch., 
1900. 

V. Recklinghausen: Handb. d. allg. Path. d. Kreislaufs u. d. Ernahrung, Stuttgart, 
1883. 

Rokitansky: Lehrb. d. path. Anatomic, Wien, 1855. 
Roser, K. : Entziindung und Heilung, Leipzig, 1886. 
Ribbert: Das pathologische Gewebswachsthum, Leipzig, 1896. 

Samuel: Der Entzlindungsprocess, 1873; Entzlindungsherd und Entzlindungshof. 
Virch. Arch., 121 Bd. ; Ueber anamische, hyperamische u. neurotische Entziindung. 
lb., 121 Bd. ; Die Selbstheilung der Entzlindungeu und ihre Grenzen. lb., 126 
Bd., 1891. 

Thoma: Ueber die Entziindung. Berl. klin. Woch., 1886; Pathol. Anat., i., 1894. 
Virchow: Cellularpathologie u. Handb. d. spec. Path., i., 1854; Die Rolle der Gefasse 

und des Parenchyms bei der Entziindung. Virch. Arch., 149 Bd., 1897. 
Weiss: Beitrage zur Entzlindungslehre, Wien, 1893. 
Woronin: Untersuchungen liber die Entziindung, Moskau, 1897. 

Ziegler: Historisches u. Kritisches liber die Lehre von der Entziindung. Beitr. v. 
Ziegler, xii., 1892: Entziindung. Eulenburg's Realencyklop., vii., 1895; Inflam- 
mation, Twentieth Century Practice of Medicine, xvi.. New York, 1899. 

{Migration of Leucocytes, and Inflammatory Exudation.) 

Appert: Der Einfluss des Chinins auf die Auswanderung der weissen Blutkorperchen 

bei der Entziindung, Virch. Arch., 71 Bd., 1877. 
Arnold: Ueber Diapedese. Virch. Arch., 58 Bd., 1873; Verhalten der Biutgefasse 

bei der Emigration weisser Blutkorper. lb., 62 Bd., 1875; Ueber die Kittsubstanz 

der Endothelien. lb., 66 Bd., 1876; Saftbahnen des Bindegewebes. lb., 68 Bd., 

1876. 

Binz: Der Antheil des Sauerstotfes an der Eiterbildung. Virch. Arch., 59 Bd., 1874, 
and 73 Bd., 1878; Verhalten der Auswanderung farbloser Blutzellen zum Jodo- 



INFLAMMATORY EXUDATION. 



321 



form. lb., 89 Bd., 1882; Zur Salicylsaure- imd Chininwirkung. Arch. f. exp. 

Path., vii., 1877; Ueber einige Wirkungeii atherisclier Oele. lb., viii., 1877. 
Borisow: Chemotakt. Wirkung verscli. Subst. Beitr. v. Ziegler, xvi., 1894. 
Bunzel: Eiufluss d, vasomotor, Nerven auf die Entziindung. Arch. f. exp. Path., 37 

Bd., 1896. 

Cohnheim: L. c, Untersuchungen liber die embolischen Processe, Berlin, 1872. 
Dekhuyzen: Ueber Emigration v. Leukocyten. Verb. d. Anat. Ges., Jena, 1891. 
Disselhorst; Emigration farbloser Zellen aus dem Blute. Yirch. Arch., 113 Bd., 1888. 
Eng-elmann : Verb. d. Blutgefassendothels bei Aus^Yanderung farbl. Blutkorp. Beitr. 

V. Ziegler, xiii., 1893. 
Goecke: Exper. Entzundung der Hornhaut. Beitr. v. Ziegler, xx., 1896. 
Hauser: Entsteli. d. librinosen Exsiidates bei d. crouposen Pneumonie. Beitr. v. 

Ziegler, xv., 1894. 

Heid.enh.ain: Ueber Lymphbildung. Verb. d. X. internal, med. Congr., ii., Berlin, 
1891; Histologie u. "Physiologie d. Diinndarmschleimhaut. Arch. f. d. ges. Phrs., 
43 Bd., Suppl.-Heft, 1888; Versuche u. Fragen zur Lehre v. d. Lymphbildung. "^Ib. 
49 Bd., 1891. 

Heller: Ueber die feineren Yorgange bei der Entzundung, Erlangen, 1869. 
Hoffmann, F. A.: Eiweissgehalt der Ascitestliissigkeiten. Virch. Arch;, 78 Bd., 1879. 
Hoppe-Seyler : Ueber serose Transsudate. Yirch. Arch., 9 Bd., 1856. 
Klemensiewicz: Fundamentalversuche iiber Transsudation, Graz, 1883; Entzundung 

u. Eiterung. Festschr. f. Rollet., Jena, 1893. 
Kronaclier: Die Aetiologie u. d. Wesen der acuten eiterigen Entzundung, Jena, 1891. 
Lassar: Ueber Oedem u. Lymphstrom bei der Entzundung. Yirch. Arch., 69 Bd., 

1877. 

liavdowski: Auswanderung farbloser Blutelemente. Yirch. Arch., 96 Bd. : Die Aus- 
wanderung d. Leukocyten u. die Frage nach dem Schicksale derselben. lb., 97 Bd., 
1884. 

Liowit: Bezieh. d. Blutgefassendothels zur Emigration. Beitr. v. Ziegler, xvi., 1894. 
Maximow: Thermoelektrische Messung von Entziindunffsherden. Wiener med. 
Jahrb., 1886. 

Middeldorpf u. Goldmann: Exp. Untersuchungen lib. Croup u. Diphtheric, Jena, 
1891. 

PekeliLaring- : Diapedese d. farblosen Blutkorp. bei d. Entzlindung. Yirch. Arch., 
104 Bd., 1886. 

Ranvier: Traite techn. d'histologie, Paris, 1875-88; Beitrag z. Lehre v. d. Entzundung 
u. den dabei auftretenden corpuscularen Elementen. Yirch. Arch., 72 Bd., 1878. 

V. Recklinghausen: Das L3'mphgefasss3^stem. Strieker's Handb. d. Gewebelehre; 
Ueber Eiter und Eiterkorpercheu. Yirch. Arch., 28 Bd., 1863. 

Ribbert: Zur Anatomic der Lungenentziindung. Fortschr. d. Med., xii., 1894. 

Schklarewski: Zur Extravasation der Aveissen Blutkorperchen. Pfliiger's Arch., i., 
1869. 

Schumacher: Pharmakol. Studien liber die Auswanderung der farblosen Blutkorper- 
chen. Arb. a. d. pharmakol. Institut zu Dorpat, x., 1894. 

Senftleben: Verschluss d. Blutgefasse nach d. Unterbindung. Yirch. Arch., 77 Bd., 
1879. 

Siebel: Ueb. d. Schicksal v. Fremdkorperu in d. Blutbahn. Yirch. Arch., 104 Bd., 
1886. 

Stohr: Ueber Mandeln u. Balgdriisen. Yirch. Arch., 97 Bd., 1884. 

Thoma: Entzlindl. Storungen d. Capillarkreislaufs bei TTarmbliitern. Yirch. Arch., 

74 Bd., 1878; Die Ueberwanderung farbloser Blutkorper v. d. Blut- in d. Lymph- 

gefasssystem, Heidelberg, 1873. 

See also 91-94. 

§ 91. The cellular and fluid exudates secreted by tlie vessels collect first 
in tlie^mmediate neighborhood of the vessels (Fig. 180), but soon spread 
out in the vicinity, mass themselves in the lymph-spaces of the tissue, and 
thus form a tissue=infiltrate (Figs. 181, e ; 182, Z>; 185, p). AAHaen the 
exudate is very abundant it may spread into and infiltrate the neighbor- 
ing sound tissue that has not been injured by the inflammatorj^ irritant. 
This infiltration may be so marked that new disturbances of circulation 
and nutrition may be produced, and the area of tissue -degeneration and 
inflammatory exudation becomes increased in extent. 

The exudate present in a tissue may he in jxirt absorbed by the tissue- 



322 



INFLAMMATION. 



elements, so tliat they become swollen, seixirated from their sii™^^^^ 
(Fig. 181, c, d), and not rarely contain drops of Jimd {d) which are com- 




Fir 181 -Recent purulent raeninffitis (Miiller's fluid, hematoxylin), a \rachnoid : Z>, suDarachaoideal 
FIG. 181. Kecem P^^^J' desquamated endothelium; c, pus -corpuscles. X oOO. 

monlY desi^-nated vacuoles. There often occurs also a complete dissolu= 
tion of the^tissue=elements in the exudate, especially of the connective- 
tissue cells (Fi^'. 183, dj), and not infrequently, also, of the intercellular 




FIG 18-' -Ha^matogenous staphylococcus myositis (alcohol, haematoxylin-eosin-) a. Trr.nsversely cut 
J^IG. ib~. "^^™^;;;-J,jj,dles; t pumlent, c, seropurulent, partly coagulated exudate, a 4o. 

substance. In this way both brain and muscle tissue, as well as ordinary 
connective tissue, may become completely liquefied in the course ot in- 
flammation. , . . ^1 • 

If dead cells become saturated with lymph containing fibrinogen, and 
if fibrin-ferment is formed, the liquefaction of the infiltrated tissue may 



VARIETIES OF INFLAMMATION. 



323 



be preceded by a coagulation, whereby Ibe cells become changed partly 
into homogeneous masses without nuclei, and partly into granular and 
fibrillar masses. 




Fig. 183.— Section through the border of a blister caused by a burn (alcohol, carmine), a. Horny 
layer; &, rete Malpighli ; c, normal papilhe ; r/, swollen cells, some of whose nuclei are still visible though 
pale, while others have been destroyed ; c, interpapillary epithelial cells, the deeper ones intact, those of the 
upper layers are drawn out longitudinally and in part are swollen and have lost their nuclei ; /, total 
liquefaction of the cells ; g, interpapillary cells, without nuclei, swollen and raised from the cutis ; lu total 
degeneration of interpapillary cells which have been raised from ttie cutis ; /f, coagulated exudate (flbrin) 
lying beneath the uplifted epithelium ; i, flattened papilla) infiltrated with cells. X 150. 



If the exudate within an organ — for example, in a muscle — lies chiefly 
in the supporting tissue, while the specific parenchyma appears but little 



I' -ft •& • 




Fig. 184.— Parenchymatous hepatitis (Flemmintr's solution, safranin). a. Liver-capsule; h, hver-rods show- 
ing fatty degeneration ; c, liver-cells showing total degeneration. X 300. 



changed, the inflammation is designated as an interstitial inflammation 
(Fig. 182, b). If, on the other hand, the degeneration of the specific 



324 



INFLAMMATION. 



tissue — i.e., the epithelium of the kidney tubules, the liver-cells (Fig. 
184, b, c), or the contractile substance of the muscles — is the most 
prominent feature of the process, and if these parts appear saturated 
with exudate, the condition is called a parenchymatous inflammation. 

A'VTien the seat of an inflammation is on the surface of an organ, it is 
termed a superficial inflammation (Fig. 185). If the exudate gains 
free access to the surface and flows from the same mixed with desqua- 
mated portions of the tissue (Fig. 185, d, e, f, f^, g, Ji), the inflammation 
is called a catarrh. If the pouring out of a fluid exudate on the surface 
of the skin or mucous membrane is hindered by a coherent horny epithe- 
lial layer (Fig. 183, a), and if beneath this covering there are formed cir- 
cumscribed collections of fluid, in which the deeper and softer layers of 



I- - ■' 



c cd 

1^ l' I\ 



Fig. 185.— Mucous catarrh of a bronchus (Miiller's fluid, aniline-brown) . a. Ciliated epithelium: Oj. 
deeper cell-layers; goblet-cells; c, cells showing marked mucous degeneration; Cj, mucoid cells with 
mucoid nuclei ; d, desquamated mucoid cells ; e, desquamated ciliated cells : f , layers of drops of mucus ; 
/i, layer consisting of thready mucus and pus-corpuscles; (/, duct of mucous" gland filled with mucus and 
cells; 7;, desquamated epithelium of the excretory duct ; intact epithelium of the duct ; ^, swollen hyaline 
basement-membrane: Z, connective tissue of the mucosa, infiltrated with cells in part; ?/). dilated blood- 
vessels; ??, mucous gland filled with mucus: »i, lobule of mucous gland without mucus ; o. wandering 
cells in epithelium ; p, cellular infiltration of the connective tissue of the mucous glands. X 110. 



the epithelium dissolve (Fig. 183, d, /, K), the lesions thus produced 
are called vesicles and blisters. When the exudate from serous surfaces 
collects in the body cavities, there are formed in the latter inflammatory 
effusions, which not rarely reach a very large size, distend the affected 
cavity, and compress the organs contained within it. 

It is customary to express the occurrence of an inflammation of an 
organ by adding the termination '^itis^' to the Greek name of the organ. 
Thus, for example, are formed the terms endocarditis, myocarditis, peri- 
carditis, pleuritis, peritonitis, encephalitis, pharyngitis, keratitis, orchi- 
tis, oophoritis, colpitis, metritis, hepatitis, nephritis, amygdalitis, glos- 
sitis, and gastritis. The ending ^^itis'' is also sometimes affixed to the 
Latin names, as, for example, conjunctivitis, tonsillitis, and vaginitis. 
To denote an inflammation of the serous covering of an organ or of the 



THE ORIGIN OF THE CELLS IN THE EXUDATE. 



325 



tissues immediately about it tlie prefixes ''peri" aud '^para^' are placed 
before the Greek uames with the termiuatiou "itis. " Thus, for example, 
are formed the words perimetritis, parametritis, periproctitis, perityph- 
litis, paranephritis, and perihepatitis. 

For certain forms of inflammation especial names are used, as, for 
example, inflammation of the lungs is called pneumonia, and inflamma- 
tion of the palate and tonsils, angina. 

Since Colmheim taught that the migration of leucocytes en masse is an important 
feature of inflammation and serves as a source for the ceils in the exudate, tlie ques- 
tion of tlie origin of the cells present in the exudate of acute inflammations has been 
many times the subject of discussion. While some have regarded all the cells in the 
exudate as extravasated leucocytes, others have held that the leucocytes arising from 
the blood-stream form only an unessential element, and that the main part of the cells 
in the exudate have arisen on the spot from the tissue " irritated " by the cause of the 
inflammation. 

Strieker held the opinion that the swelling and hardening of the tissues in inflamma- 
tion are not caused b}" the collection of exudate, but by the swelling of the cell-reticulum 
which was thought to traverse the tissues; and that these changes represent a phenome- 
non of growth of the cells and their processes which is characterized hj swelling. The 
cellular exudate — that is, pus — he accounts for parti}" through the segmentation and 
division of the cell-reticulum swollen by the inflammation, and parti}' through a trans- 
formation of connective-tissue fibrilla) into pus-corpuscles. Heitzmann regarded the 
inflammatory tissue-changes as a reversion of the tissue to the embryonal condition, and 
believed that the living material is not contained in the cells alone, but inflltrates the 
entire ground-substance, and increases, in the progress of an inflammation, with the 
liquefaction of the ground-substance. Connective-tissue cartilage and bone become 
resolved during inflammation into those elements from which the}' are formed — i.e., 
into cells — which then immediately reproduce their kind. Graintz believes that botli 
the cellular infiltrate aud pus are formed without any participation of the leucocytes 
worth mentioning. Everywhere in the tissue, according to his view, there lie concealed 
in gi-eat numbers cells, which he designates slumber-cells, and which are not affected 
by our nuclear stains and therefore not recognizable (according to him, only from five 
to ten per cent, of the tissue-cells are known to us) ; these cells awake in inflammation, 
and again come into sight — that is, increase in size, stain with nuclear stains, and there- 
fore again become recognizable. 

According to the results of an unprejudiced and careful examination of inflamed 
tissues, there can be no doubt that the description of the origin of the inflammatory in- 
filtrate given by Strieker, Heitzmarm, Grawitz, and their pupils, does not correspond to 
the conditions as they actually exist. The cells which lie in recently inflamed tissue 
consist in part of leucocytes which have wandfered from the vessels and in part of 
tissue-cells which are more or less degenerated, ^d are often separated from the under- 
lying tissues. Later, to these there are adde^ newly formed cells which have arisen 
through the division of pre existing tiss«e*cells. 



Literature. 

{The Processes Occurring in the Tissues during Inflammation, and the Origin 
of the Cells in the Exudate. ) 

Alexander-Levin: Histologic d. acut. bakteriellen Entzliudung. Arb. a. dem Inst. 

V. Baumgarten, i., 1891. 
Baumg-arten: Herkunft d. in Entzlindungsherden auftret. lymphkorperart. Elemente. 

Cbl. f. allg. Path., i., 1890. 
Bottcher: Entstehung der Eiterkorperchen bei der traumatischen Keratitis. Virch. 

Arch., 58 Bd., 1873; Ueber die circumscripte Keratitis. lb., 62 Bd., 1875. 
Cattani: Ueber die Reaction der Gewebe auf specifische Reize. Beitr. v. Ziegler, vii., 

1891. 

Coen: Veranderungen der Haut nach Einwirkung von Jodtinctur. Beitr. v. Ziegler, 
ii., 1887. 

Eberth.: Entzilndung d. Hornhaut. Unters. a. d. path. Inst, in Ziirich, Leipzig, 1874 
and 1875; Kern- u. Zelltheilung bei Entzundung. Internat. Beitr., Festschr. f. 
Yirchow, ii., Berlin, 1891. 

Ehrhardt: Muskel veranderungen bei d. Trichinose. Beitr. v. Ziegler, xx., 1896. 
19 



326 



INFLAMMATION. 



Grawitz: Die Entwickelung der Eitci'uiiusk'hre. Dent. med. Wocli., 1889 : TTistolog. 
Vemnderimgen bei der eitrigen Eiit/.undung. Vircli. Arch.. 118 Bd., is.si); Atlas 
der patliol. Gewebelelire, Berliu, 1898, Eiitzunduiiii' d. llornhaut. Viicli. Arch., 
144 Bd., 1896. 

Griinwald; Zellen ini Auswiirf ii. entzlindl. Aiisschwitzungen. Virch. Arcli. lo8 
Bd., 1899 

'Key u. Wallis: Exj). Enters, iib. d. Entzuiidimg d. llornhaut. Yirch. Arch., .-)."■) Bd., 
1872. 

Krafft: Znr Histogenese des periostalen Callus. Beitr. v. Ziegler, i., 1886. 
Marchand ■ Untersiich. iiber die Einheilung von Eremdkorpern. Beitr. v. Zie<iler, iv., 
1888. 

Neumann: Die Pikrokarminfarbung ii. ilire Auwendung auf die Entziindungslehre. 

Arch. f. mikr. Anat., xviii., 1880. 
Nikiforoif: Ban ii. Entwickelung des Grannlatiousgewebes. Beitr. v. Zieixler, viii., 

1890. 

Podwyssozki : Regeneration der Driisengewebe. Beitr. v. Ziegler, i., ii., 1884-88. 
Roemer. Die chemische Rcizbarkeit thierischer Zellen Virch. Arch., 138 Bd., 1892. 

Strieker: Stndien a. d. Institute f. 
exp. Pathologic, Wien, 1870; Ver- 
schied. Aufsatze in den Wi(Mier 
med. Jahrb. a. d. J., 1871-^3: All- 
gem. Pathologic, Wicn. 18 7 7-88. 
Weig-ert: Die Yirchow'schc Entzi'm- 
dungstheorie ii. d. Eiterungslehre. 
Fortschr. d. Med., vii., 188^9. 
Ziegler: Exp. Enters, liber die Iler- 
kunf t der Tube r k e 1 e 1 e ni e n t e. 
Wlirzburg, 1875; Enters, liber 
patholog. Bindegewebs- u. Gctass- 
neubildinig. Wlirzburg. 1876; 
Eeber die Betheiligung der Ecu- 
koc3'teu an der GcAvebsneubildung. 
Verb. d. X. intei'nat. med. C'onur.. 
ii,, Berlin, 1891; Eeber die Er^ 
sachen der pathol. Gcwcbsncubil- 
dung. Festschr. f. Vircliow. ii., 
Berlm, 1891; Historisches u. Krit- 
isches liber die Lehre von der 
Entzlinduug. Beitr. v. Zieaier, 
xii., 1892. 

See also 90 and 93. 



L 

r- 



m4 



Fig. Purulent desquamative catairli of tlie tra- 

chea in measles (alcohol, hfematoxylin. eosin ) . (U Layer 
of pus-corpuscles and desquamated epithelium ; h, intact 
deepest layer of epithelium ; c, basement-membrane : 
d, hyperaemic and inflltrated cotinective tissue of the 
mucosa ; e, inflltrated submucosa with mucous glands. 
X 100. 



§ 92. Both the local tissue- 
degeneration and tlie exudation 
may vary greatly in different 
cases, and there may be distin- 
guished accordingly different 
forms of inflammation. 

If the exudate consists essen- 
tially of fluid, while the cellu- 
lar constituents are insignificarit, 
it is called a serous exudate. 
When contained within a tissue 
— for example, within the skin 
and subcutaneous tissue, or in 
the lungs— there results an in= 
flammatory oedema. The es- 
cape of the fluid on the free 
surface of a mucous or serous 
membrane gives the picture of 
a serous catarrh ; circumscribed 
collections of fluid beneath the 



CATARRHAL INFLAMMATION. 



327 



horny layer of the epidermis with the liquefaction of the soft layers of 
epithelium lead to the formation of vesicles and blisters with clear con- 
tents (Fig. 183, d,f), ,^ 

When the exudation of fluid on the surface of a mucous membrane is 
associated with a marked mucoid degeneration of the superficial epithe- 
lium (Fig. 185, h, c, cj, and of the mucous glands {n), there arises a 




Fig. 187.— Catarrhal secretion of diflferent mucous membranes. -4, Secretion from mucous membranes 
with columnar cells ; B, from the mouth ; C, from the bladder. 1, Round cells (pus-cells); 3, large round 
cells with bright nuclei, from the nose ; 3, mucoid columnar cells from the nose ; 4, spirillum from the nose ; 
5, mucoid cells with cilia, from the nose ; 6, goblet-celJs from the trachea; 7, round-cells with spherules of 
mucus from the nose ; 8, epithelial cells containing pus-corpuscles, from the nose ; 9, fatty cells ; 10, cells 
containing coal-pigment, from the sputum ; 11 and 13, squamous epithelium from the mouth ; 13, mucoid 
pus-corpuscles: 14!,' micrococci ; 15, bacteria; 16, leptothrix huccalis; 17, spirochcete denticola ; 18, super- 
ficial, 19, middle layer of bladder epithelium ; 30, pus-corpuscles ; 31, seliizomijcetes. X 400. 

mucous catarrh (d, f, f^, g). If a marked desquamation of the epithe- 
lium, with or without a mucoid change, occurs (Fig. 186, a), the condi- 
tion is termed a desquamative catarrh ; and such a process may occur 
not only on mucous membranes, but also in the respiratory parenchyma 
of the lungs, on serous surfaces (Fig. 180, in the kidney-tubules, 
etc. If many pus-corpuscles are present in the exudate it may be spoken 
of as a desquamative purulent (Fig. 186, a), or finally as a pure puru- 
lent catarrh, in which condition the exudate becomes white or yellow- 
ish-white, milky or creamy. 

The form and character of the cells of a catarrhal secretion vary with 
the location and the variety of catarrh (Fig. 187). Bacteria are often 
present in the cells of the exudate (Fig. 187, i, 1^, 15, 16, 17, 21). 

If in a fluid exudate thei'e occurs a deposition of fibrin or coagula- 
tion, there are formed fibrinous and serofibrinous exudates, which are 
often designated as croupous. These occur chiefly upon the surface of 
serous and mucous membranes, and in the lungs ; but masses of fibrin 



328 



INFLAMMATION. 






may be formed in tissues infiltrated with exudate, as w.ell as in lymph- 
vessels. 

On the mucous membranes the fibrinous exudates form Tvhitish 
patches and coherent membranes, which sometimes lie upon them only 

loosely, but at other times are firmly 
attached to the underlying surface. 
In the serous ca^'ities the fibrinous 
coagula float in the form of flakes in 
the fluid portion of the exudate, or 
form a firmly attached deposit ui^on 
the surface of the membranes. Such 
deposits consist at times only of thin, 
attached films or granules which 
give to the wii)ed-off surface a 
cloudy, lustreless, rough, or gi-anu- 
lar ai3i3earance ; at other times of 
larger yellowish or yellowish-red, 
firm membranes, which often give 
to the surface a felted or villous 
appearance (cor villosum). In the 
lung, croupous inflammation leads 
to a filling of the alveoli with a 
coagulated mass, in consequence of 
which the lung acquires a firm con- 
sistence. 

On mucous surfaces the formation 
of croupous membranes takes place 
when the epithelium is ab^eady des- 
quamated and the connective tissue, 
at least in part, is exposed: but tis- 
sues covered with epithelium may 
also become the seat of fibrinous de- 
posits extending from denuded areas. 
The desquamation of the epithelium, 
in such a case, may follow gradually, or at other times more rapidly 
through the lifting up of whole layers of epithelium (Fig. 188, h), 
which are either well 
preserved or already 
degenerated or necro- 
tic, and infiltrated with 
exudate (Fig. 190, a). 
The exudation of 
fibrin may begin un- 
derneath the raised- 
up epithelium with the 
formation of fine 
needle -like forms re- 
sembling crystals (Fig. 
188, d), which are ar- 
ranged radially about 
a centre, in which at 
times there lies a small 

body, probably a product of the disintegration of a red corpuscle, or a 
blood-plate. Very soou there form thicker or thinner threads (Figs. 



Fig. 188.— Acute hemorrhagic fibrinous in- 
flammation of the trachea, caused by vapor of 
ammonia (Miiller's fluid, htematoxyUn, eosin). 
o. Superficial layer of the connective tissue of 
the mucosa, with greatly dilated blood-vessels 
and extravasated red blood-cells ; /^ deep layer 
of epithehum raised up in tnto; c, desquamated 
epithelial cells ; c7, ha?morrhagic fibrinous exu- 
date with radiating, crystal-like masses of fibrin, 
in part proceeding from small, colorless spher- 
ules. X 300. 




Fig. 189.— Croupous membrane from the trachea, a. Section 
through membrane; /), uppermost layer of the mucosa infiltrated 
with pus-corpuscles (c?); c, fibrin threads and granules; d. pus-cor- 
puscles. X 2.50. 



FIBRINOUS INFLAMMATION. 



329 



189, c : 190, h, c) which enclose a larger or smaller number of leucocytes 
and red blood-cells. The arrangement of the threads is usually reticu- 
lar, but the thickness of the network and the size of the meshes vary 
greatly. AVhen there is unequal development of the fibrin threads and 
strands, the principal strands sometimes lie parallel with the surface 
of the mucous membrane (Fig. 189, «), sometimes perpendicular to it 




♦ Section from an inflamed uvula co\ tn-ecl with a stratified fibrinous membrane, from a case 

01 diphtheritic croup of the pharyngeal organs C^Ililler's fluid, hiematoxvlin, eosin) . o. Surface laver of 
coagulum, consisting of epithelial plates and flbrin and containinsr numerous colonies of cocci ; &. second 
layer of coagulum, consisting of flne-meshed flbrin network enclosing leucocytes ; c, third laver of coagulum, 
lying upon the connective tissue, and consisting of a wide-meshed reticulum of fibrin enclosine: leucocytes ; 
«, connective tissue infiltrated with cells ; r. infiltrated boundary laver of the connective tissue of the mucous 
membrane ; / , iieaps of red blood-cells ; (y, widely dilated blood-vessels : J/, dilated Ivmph-vessels filled with 
fluid, flbrin and leucocytes; i, duct of a mucous gland distended with secretion ; Tf," transverse section of a 
gland ; flbnn reticulum in the superflcial laver of connective tissue. X 45. 



(Fig. 190, c). Thick fibrinous membranes frequently show a distinct 
stratification (Fig. 190, a, Z>, c), indicating that their formation has oc- 
curred in successive batches pushed up from below. 

When a mucous membrane becomes the seat of a deposition of fibrin, 
the underlying connective tissue is always more or less hypersemic (Fig. 
190, g), cedematous and swollen, infiltrated with leucocytes (Figs. 190, 
d, e; 191, e), and usually contains here and there also thready fibrin 
precipitates (Figs. 190, I; 191, /). Very often the tendency to the 



330 



INFLAMMATIONo 




FiOt 191 —Croupous tracheitis. Section through the connective tissue of the mucosa (carmine and 
flbrin-stain)." a, 7j, c, d. Blood-vessels with fibrin precipitates- e, oedematously swollen connective tissue 
with leucocytes ; /, connective tissue with fibrin-threads. X 500. 




FIG. 193.-Fibrinous pleuritis (alcohol, Van Gieson's). a. Connective tissue; h desquamated epithelium; 
c, thick, homogeneous, d granular layer of fibrin with leucocytes. X lOU. 



FIBRINOUS EXUDATION. 



331 



precipitation of fibrin is manifested also within the blood-vessels (Fig. 
191), inasmuch as these contain at times tangled threads and rods of 
fibrin (Fig. 191, h), at other times fibrin-needles grouped in stellate 



forms or in clusters (a, c, 
endothelial cells or leuco- 
cytes, or from blood-]3lates, 
or radiate from portions of 
the vessel -wall where the 
endothelium is lost. Like- 
wise, fibrin - threads may 
be also found in the dilated 
lymph -vessels, in associa- 
tion with fluid and cellular 
exudate (Fig. 190, h). 

On the serous membranes 
the deposits of fibrin ap- 
pear partly in granular 
(Fig. 193, d) and thready 
(Fig. 192, d, e), or in thick, 
homogeneous masses (Fig. 
193, c), or even in the form 
of ribbon-like bands. Here 
also the epithelium is exfo 
liated at the point of dei)o- 
sition (Figs. 192, d, e ; 193, 
c), but may be preserved 
in patches and covered over 
with fibrin (Fig. 192, c). 
The connective tissue of 
serous membranes in croup- 
ous inflammation is some- 
times more, sometimes less 
infiltrated, and may con- 
tain leucocytes and fibrin, 
both in the congested ves- 
sels themselves (Fig. 191, 
g) and in the connective- 
tissue spaces (Figs. 191, e, 
/; 194, c). More marked 
exudations of fibrin ux^on 
the surface of serous mem- 
branes may produce thick, 
felted deposits, the formed 
elements of which consist 
of thready fibrin and pus 
corpuscles (Fig. 194, d, e), 
as well as micro-organisms 
(1)). An abundance of pus - 
corpuscles gives to the 
exudate a Jibrino])urulent 
character, the yellowish de- 
posits becoming more whit- 
ish in color. 

Fibrinous exudates in the 



d), which often proceed from degenerated 




Fig. 194.— Fibrinopurulent diplococcus pleuritis in a three-year- 
old child (formalin, flbrin-stain). o, Inflamed pleura: diplo- 
cocci ; f, fibrin ; c?, 6, hbrinopurulent exudate. X 500. 



332 



INFLAMMATION. 



lungs are characterized by the formation of a more or less close network 
of fibrin -threads (Fig. 195, h), in whose meshes and in the immediate 
neighborhood of which lie leucocytes and usually also red blood-cells (e), 
mingled with desquamated epithelium. In the first stages there are also 
found occasionally globular, wreath-shaped precipitates of fibrin joined 
together in rows. Fibrin-threads may develop also in and upon dead 
epithelium ( Hauser ) . 

In the Mdneys deposits of fibrin may occur in the form of fine threads 
or hyaline masses in the urinary tubules and glomerular capsules. In 
the lymph-glands fibrin-threads are formed particularly in the lymph- 
channels. 

Hasmorrhagic exudate — that is, an exudate containing large num- 
bers of red cells — occurs especially in connection with the exudation of 
fibrin. The exudate of croupous pneumonia constantly contains a larger 
or smaller number of red blood-cells (Fig. 195, c), and likewise in fibrin- 




FlG. 195. 



-Croupous pneumonia. Red bepatization of tbe (alcobol, carmine, flbrin-stain) . 
trated alveolar septa ; ?), fibrinous exudate ; c, red blood-cells. X 300. 



a, Infll- 



ous pericarditis and pleuritis great numbers of red blood -cells not infre- 
quently escape from the vessels. Hsemorrhagic inflammations occur not 
infrequently in the central nervous system, in lymph-glands, in the skin 
and kidneys. In the last case the blood escai)es from the glomerular 
vessels. 

The serous, fibrinous, and serofibrinous inflammations are caused by 
thermal and chemical influences, as well as by bacteria; but are most 
frequently the result of infection, particularly of infection with the Dip- 
loeoccus pneumonice (Fig. 194, h) and the Bacillus dipJitherice. The former 
causes particularly croupous inflammations of the lungs and pleura, the 
latter gives rise to fibrinous inflammations of the throat, palate, and 
respiratory passages. 

Neumann holds the opinion that in recent fibrinous inflammations of the serous 
membranes the hyaline bands and lumps on the surface of the membrane are not exu- 
dative fibrin, but represent layers of connective tissue that have undergone a fibrinoid 
degeneration. I cannot subscribe to this view, but agree rather with the majority of 



CATARRHAL, SEROUS, AND FIBRINOUS INFLAMMATION. 333 



writers who have expressed opinions upon this subject that the deposits are exuda-- 
tive tibrin. The ilhistrations which Neumann has presented in his work are in no man- 
ner confirmatory of his view, but enable us rather to affirm that Neumann had before 
him in his preparations exudative fibrin. In very severe inflammations fibrin may 
indeed be precipitated in tlie connective tissue of the serous membranes; and, when 
treated with stains, may occasion a peculiar staining of the tissue, but in such a case 
we have to deal with a deposit of exudative fibrin, and not with a fibrinoid degenera- 
tion of connective-tissue fibres. 



Literature. 

(Cat((r)-h(d, Serous, and Fibn7ious Inflammation, and Formation of Inflam- 
matory Blebs, ) 

Abramow: Fibrinose Entziind. d. serosen Haute. B^eitr. v. Ziegler, xxiii., 1898. 
Appel: Ueb. d. Herkunft. d. Fibrins auf serosen Hauten. Inaug.-Diss., Gottingen, 
1895. 

Arnold: Morphologic d. extravascul. Gerinnung. Virch. Arch., 150 Bd., 1897. 
Bag-insky: Diphtheric u. diphtheritischer Croup, Wien, 1898. 
Baumgarten: Pathogenese der diphtherischen Membran. Berl. klin. Woch., 1897. 
Borst: Fibrinose Exsudation u. fibrinoide Degeneration. Zeit. d, Phys.-med. Ges. 
Wiirzburg, 1897. 

Cornil: Inflamm. des membranes sereuses. Arch, de med. exp., 1897. 
Ernst: Ueber das Vorkommen des Fibrins in Nierencylindern. Beitr. v. Ziegler, xii., 
1893. 

Gay lord: Fibrinous Exsudates. Jour, of Exp. Med., iii., 1898. 
Georg-iewsky : Fibrin. Entziind. seroser Haute. Beitr. v. Ziegler, xxv., 1899. 
Graser: Die r- te Verklebung seroser Haute. Langenbeck's Arch., 50 Bd., 1895. 
Hauser: Pathol. Fibringerinnung. Deut. Arch. f. klin. Med., 5.0 Bd., 1893: Entsteh. 

d. fibrin. Exsudates bei dor croup. Pneumonic. Beitr. v. Ziegler, xv., 1894; Gerin- 

nungscentren. Virch. Arch., 154 Bd., 1898. 
Heinz: Jod u. Jodverbindungen. Virch. Arch., 155 Bd., 1899; Entsteh. d. Fibrins. 

II)., 160 Bd., 1900. 
Herxheimer: Fibrinose Entziindungen. Virch. Arch., 160 Bd., 1900. 
Heubner: Ueber die diphtheritische Membran. Jahrb. f. Kinderheilk., xxx., 1889; 

Verb. d. Congr. f. inn. Med., viii., 1889. 
Jatta: Genese de la fibrine dans les inflam. de la plevre. Arch. ital. debiol., xxxi., 

1898. 

Israel: Die anamische Nekrose der Nierenepithelien. Virch. Arch., 123 Bd., 1891. 

Kossel: Ueber Schleim und schleimbildende Stoll'e. Deut. med. Woch., 1891. 

Kramer: Veninderungen d. Rachen- u. Kehlkopfschleimhaut b. Diphtheric. Inaug.- 
Diss., Freiburg, 1890. 

Marchand: Fibrinose Exsudation bei Entziindungen. Virch. Arch., 145 Bd., 1896. 

Middeldorpf u. Goldmann: Exp. u. path.-anat. Unters. lib. Croup u. Diphtheric, 
Jena, 1891. 

Miiller: Veriind. d. Blutkorp. bei extravascul. Gerinnung. Cbl. f. allg. Path., viii., 
1897. 

Neumann: Pikrokarminfarbung und ihre Anwendung auf d. Entziindungslehre. 
Arch. f. mikr. Anat., xviii., 1880; Fibrinoide Degeneration d. Bindegewebes bei 
Entziindungen. Virch. Arch., 144 Bd. ; Fibrinoide Degenerat. u. fibrin. Exsuda- 
tion. lb., 146 Bd., 1896. 

Oertel : Pathogenese der epidemischen Diphtheric, Leipzig, 1887. 

Ribbert: Zur Anatomic der Lungeuentziindung. Fortsclar. d. Med., xii., 1894. 

Saltykow : Entzimdungen der serosen Haute. Beitr. v. Ziegler, xxix., 1900. 

Schweninger: Diphtheritis. Mittheil. a. d. path. Institute in Miinchen, 1878. 

Touton: Vergl. Unters. iiber die Entstehung der Hautblasen, Tubingen, 1882. 

"Weigert: Anat. Beitr. zur Lehre von den Pockeu, Breslau, 1874: Ueber Croup u. 
Diphtheritis. Virch. Arch., 70 Bd., 1877; 72 Bd., 1878; Ueber d. pathol. Gerin- 
nuu£:svorgange. lb., 79 Bd., 1880; Methoden zur Farbung von Fibrin. Fortschr. 
d. Med., v., 1887. 

Wlassow: Die histol. Vorgange bei der Gerinnung u. Thrombose. Beitr. v. Ziegler, 
XV.. 1894. . 

Zahn: Beitrage zur pathol. Histologic der Diphtheritis, 1878. 
Zenker: Intraveuose Fibringerinnung. Beitr. v. Ziegler, xvii., 1895. 
Ziegler: Ueb. d. Entziindung der serosen Hau^^e. Beitr. v. Ziegler, xxi., 1897- 
See also 90 and 93. 



334 



INFLAMMATION . 



§ 93. Wlieu the inflaiiiiuatory exudate is made uj) chiefly of leuco- 
cytes, there is i^roduced withiu the tissue a small=cened infiltration 




Fig. 196.— Purulent bronchitis, peribroiicliiris. and peribroncMiial bronohopneumnnia in a child one year 
and three months old (Miiller's fluid, hieiiiat'ixylin. eosin). f(. Purulent, ?*. nuicoid bronchial contents; 
c, Oi. bronchial epithelium intiltrated with round cells and partly de.-,iuamated ; */. intiltratetl bronchial 
wall with o-reaily dilated bl.iud-vfsst'ls ; ( . infiltrated peribronchial and ]ieriarterial connective tissue; f. al- 
veolar septa, in part infiltrated witli celW: i/, llbrinous exudate in the alveoli; //. alveoli filled witli exudate 
rich in cells ; (, alveoli filled witli exudate containinn- few ct-lls ; /,. cro>;s-sectiou of u pulmonary artery; 
bronchial, peribronchial, and interacinous vessels showiiru' marked coULi'estion. X 43. 



(Figs. 182, 1) : 196, ^7, e, f) wliich under certain conditions may be so 
marked that the structure of the tissue is moi-e or less obscui-ed. If leu- 
cocytes are present iu large numbers in the tiuid exudate on the surface 




Fig. 197.— Section of a smallpox pustule (injected hieinatoxylin preparation). (7, Horny layer; 7<, stra- 
tum mucosum of the epidermis; (7, cutis; c. smallpox pusttUe : /, cavity of the pock, containing: at /i pus- 
corpuscles ; g, interpapillary remains of epithelium infilti'ated "with pus-corpuscles; f/, paiiiliary "bodies 
infiltrated with cells; i. umbilicatiou with thin pock cover; i'l, edge of the pock, the roof at this point con- 
sisting of the horny and transitional layers. X 25. 



PURULENT INFLAMMATION. 



335 



of a mucous membrane or external wound, there appears on the affected 
l^art a white fluid, which is called pus, and has given occasion for the 
designation of such an inflammation as a purulent catarrh (Fig. 196, a). 
A i^ersistent marked secretion is termed a hlennorrlicea. Collections of 
pus in the body cavities — for example, the i^ericardial, i)leural, or joint- 
cavities — give rise iopuriilent effusions or empyemata. If within a blis- 
ter arising through the liquefaction of the epithelial layers beneath the 
horny layer of the epidermis there takes place a marked collection of 
leucocytes, the fluid becomes more and more turbid, white, purulent, 
and the vesicle becomes changed into a pustule (Fig. 197, /,). 

The emigrating cells, particularly those in purulent intlamniations, 
which are consecxuently known as pus=corpuscles, are polynudear leu- 




Fig. 198.— Embolic abscess of the Intestinal wall witli embolic purulent arteritis, and embolic aneurism 
in cross-section (alcohol, fucbsin). a, />, c, (7, c. Layei-s of intestinal wall ; f, remains of arterial wall, cross- 
section : f/. embolus, surrounded by pus-corpuscles lying within the dilated and partly suppurating artery ; 

parietal thrombus; i, periarterial purulent infiltration of the submucosa; vein showing marked con- 
gestion. X 28. 

cocijtes. They may reach the surface of a mucous membrane both after 
the desquamation of the epithelium and while it is still intact, in that 
they are able to i^ass between the epithelial cells (Fig. 196, c, cj, and in 
tlie same manner the epithelium of the external skin may be penetrated 
by them (Fig. 197, 

When leucocytes collect in such large numbers within a tissue as to 
give it a white, gray-white, or yellowish -white color the process assumes 
the character of a purulent infiltration. Should this be followed by 
liquefaction and dissolution of the tissue the process results finally in 
tissue=suppuration and abscess=formation (Fig. 198, i) — that is, in the 
formation of a cavity filled with pus. 

When purulent infiltration and tissue-supj)uration occur on the sur- 
face of an organ — for example, on a mucous membrane (Fig. 199, d, /, 



336 



INFLAMMATION. 



g~) — the process leads to a superficial loss of substance — au ulcer. The 
formation, through suppuration, of duct-like cavities gives rise to fis= 
tulous tracts. 

The dissolution of the tissues, which is designated as suppuration, is 
possible only under the condition that they die. This tissue-necrosis is 
iisually present before the occurrence of suppuration, and is caused by 
the specific action of the agent exciting the inflammation. The tissue 
may, however, die only during the course of inflammatory infiltration 
and then liquefy. 

If an accumulation of i^us-corpuscles is associated with an abundant 
collection of fluid, the exudate is spoken of as seropurulent ; and such 
an exudate, when infiltrating the tissues, is often designated purulent 
oedema. The raiDid spread of a purulent or seropurulent inflammation 
over T\'ide areas — for example, through extensive areas of subcutaneous 
or submucosal tissues — is known as phlegmon (Fig. 200, c, d). This 
leads very often to the formation of extensive pus-cavities, in which 
there lie shreds of disintegrating tissue infiltrated with pus. 

The association of serous exudation and fibrin precipitation with sup- 
puration leads to the formation of fibrinopurulent exudates (Fig. 194, 
d, e) ; and effusions into the body-cavities, and meningeal exudates, as 
well as croupous exudates on mucous surfaces and in the lungs, and also 
phlegmons may bear this character. It is to be noted, however, that 
with the increase of supi)uration the formation of fibrin becomes de- 
creased, and the masses of coagula already present dissolve. The fibrin- 
masses infiltrated with pus are white and easily torn. 

Suppurations and the associated formation of abscesses and ulcers are 
in the majority of cases caused by bacteria, most frequently by the 
Staphylococcus pyogenes aureus, Strfpiococcus pyogenes, and the Gonococcus ; 




Fig. 199. -Suppuration and necrosis of the mucosa of the larpre intestine in dysentery (MuUer's fluid, 
haematoxyhn, eosin). Section through the mucosa (a) and submucosa (h) of the large intestine ; c, muscu- 
laris ; f?, interglandular, t/j, subglandular Infiltration of the mucosa; e, focus of infiltration in the submu- 
cosa ; /, infiltrated upper glandular layer undergoing desquamation ; g, ulcer with infiltrated base. X 

but suppurations due to Actinomyces, Bacillustyphi aMominaJis, Biplococcus 
pnenmonice, or the Bacterium, coJi commune, are not rare. The staphylo- 
cocci generally produce localized inflammations; streptococci, on the 
other hand, phlegmonous. The presence of certain bacteria (^BaciUus 



SUPPURATION. 



337 



phlegmones emphysematosw, Frankel ; Bacillus a'erogenes capstilatus, Welch) 
may cause the formation of gas (gasplilegmon). Suppuration is sometimes 
ectogenous, sometimes Ijnnj^hogenous or hgematogenous ; and in the hist 
case often bears the character of a 
metastatic process (Fig. 198). 

Of the chemical substances Avhich, 
when introduced into the tissues, can 
produce suj^puration may be men- 
tioned mercury, oil of tur|)entine, pe- 
troleum, five- to ten-per-cent. solutions 
of silver nitrate, creolin, digitoxin, 
dilute croton-oil, and sterilized cultures 
of various bacteria, in which the bac- 
terial proteins are the active agents. 
The suppurations produced by chemi- 
cal substances differ from those pro- 
duced by infection, in that they heal 
more easily, do not spread in the tis- 
sues, and do not give rise to metastases, 
and through the fact that their prod- 
ucts when inoculated possess no vir- 
ulence. 





Literature. 

{Suppuration. ) 

Buchner: Die cliemisclie Reizbarkeit d. Leu- 

kocyten ii. deren Bezieli. zur Entzimdung. 

Berl. klin. Woch., 1890; Bakterienpro- 

teine ii. deren Bezieli. z. Entzlindung. 

Cl)l. f. Chir., 1890. 
Brandenburg : Reaction der Leukocyten auf 

Guajaktinctur. Miincli. med. Woch., 

1900. 

Bunge: Zur Aetiologic der Gaspblegmonen. 
Fortschr. d. Med., xii., 1894. 

Coenen: Die Alenronat - Pleuritis. Virch. 
Arcli., 163 Bd., 1901. 

Councilman: Zur Aetiologie der Eiterung, 
Yirch. Arch., 93 Bd., 1888. 

Dmochowski u. Janowski: Eiterung erreg. 
Wirk. d. Typliusbacillus. Beitr, v. Zieg- 
ler, xvii., 1895 (Lit.). 

Dubler : Ein Beitrag zur Lehre von der Eiter- 
ung, Basel, 1890. 

Fraenkel, C: Ueber die Gaspblegmonen, Leipzig, 1893; Mlincb. med. Wocb., 1899. 
G-rawitz: Bedeutung des Cadaverins fiir d, Entstehen von Eiterung. Vircb. Arcb., 

110 Bd., 1887; Zur Tbeorie der Eiterung. lb., 116 Bd ; Histol. Verand. bei der 

eiterigen Entzlindung. lb., 118 Bd., 1889. 
V. Hibler: Spaltpilze in Zellen bei Eiterung. Cbl. f. Bakt., xix., 1896. 
Janowski: Die Ursacben der Eiterung. Beitr. v. Ziegler, xv., 1894 (Lit.); Morpbol- 

ogie des Liters. Arcb. f. exp. Path., 36 Bd., 1895. ^ 
Kaufmann: Einfluss des Digitoxins auf die Entstebung eiteriger Pblegmonen. Arcb. 

f. exp. Patb., XXV., 1889; Die Entstebung der Entzimdung, Leipzig, 1891. 
Kiener et Duclert: Formation et guerison des absces. Arcb. de med. exp., v., 1893. 
Klempner: Ueb. d, Bez. d, Mikroorganismen z. Eiterung. Zeitscbr. f. klin. Med., x., 

1885. 

Kronacher: Die Aetiologie und das Wesen der acuteu eiterigen Entzlindung, Jena, 
1891. 

Krynski; Ueber die Ursacben acut-eiteriger Entzlindungen. Cbl. f. allg. Patb., i., 
1890. 



Fig. 200.— Phlegmon of the subcutaneous tis- 
sue with formation of a vesicle through oedema 
(Miiller's fluid, haematoxylin, eosin). a, Corium ; 
h, epidermis ; c, infiltrated fat tissue ; d, focus 
of pus ; e, cellular foci in corium ; /, subepithe- 
lial vesicle due to oedema. X 30. 



338 



INFLAMMATION. 



Lemiere: Do la suppuration, Paris, 1892. 

Levy: Die niikrooi-iiauismen iler Eiterunc:. Arch. f. exp. Path., 29 Bd., 1891. 
Mliller: Stand der Eiteruni^sfraii-e. Cbl."f. Bakt., xv., 1894. 

Muscatello: Etiol. della cancrena ointisciuatica. Arch, per le Sc. Med., xx., 1896. 
Nathan: Zur Aetiologie der Eiterunii\ Langeubeck's Arch., xxxvii., 1888. 
OrthmaDn: Ueber die Ursacheu der Eiterbildung. Yirch. Arch,, 90 Bd., 1882. 
Passet: Untersuchuugen lib. d. Aetiologie d. eiterig. Phlegmone d, Menschen, Berlin, 
1885. 

Peiper: Eiterige Schmelzung der Gewebe. Vlrch. Arch., 118 Bd., 1889, 
Rinne : Der Eiterungsprocess uud seine jNIetastasen, Berlin, 1889. 
Roger: De la suppuration. Revue de Chir., 1891. 
Steinliaus : Die Aetiologie der acuten Eiterung, Leipzig, 1889. 
Welch and Nuttal: Gas Phlegmon, J. Hopkins Bull., 1892. 
See also §§ 90-92, Chapter X. 

§ 94. As was explaiued iu § 93, suppurative inflammation always 
leads to tissue -necrosis ; but this necrosis is immediatelj^ lost siglit of in the 
presence of the liquefaction and dissolution of the tissues which form 
the characteristic feature of sux^puration. In other forms of action upon 
the tissues, there may occur a more extensive tissue -necrosis, recogniz- 



Fig. 201.— Necrosis of the epithelium of tlie ei)i,!rlottis (AHiHei-'s fluid. h;vuiatt)x\iin) . a, Living epi- 
tbelium with well-stained nuclei ; h, necrotic epitheiiaiu with nuclei not staining- ; c, leucocytes lyfug iu 
the epitheliiun ; d, hypera-niic, inflamed, and inflltrated connective tissue. X 300. 



able even to the. unaided eye, which is not followed by suppuration, but 
on the other hand is characterized by the fact that the necrotic portions 
of the tissue remain unchanged for a long time, and only relativ ely late 
are removed through sequestration and sloughing or through absorption. 
Since the tissue-necrosis in such a case forms the chief feature, the con- 
dition may be appropriately designated a necrotic inflammation. 

The tissue- necrosis associated with inflammation may be caused by 
caustic chemicals, high or low temperatures, and ischsemia, as well as 
by infection (tyi)hoid fever, diphtheria, and dysentery). 

Caustic chemicals cause tissue-necrosis in the first place in those tis- 
sues with which they first come into contact ; but many substances (mer- 
curic chloride, the salts of chromic acid, cantharidin) may cause necrosis 
only after their diffusion throughout the body in the blood and lymph. 
Such necrosis takes place particularly in the kidneys, the descending 
urinary passages, and in the intestines, where the substances causing the 
necrosis are excreted. Bacteria produce necrosis at the points where 
they multiply, and where the poisonous substances formed b}^ them are 
collected in greater quantity. 




NECROTIC INFLAMMATION: DIPHTHERITIS. 



339 



The necrosis of the tissue may appear first of all as the immediate 
etfect of the injurious action, the inflammatory exudation following 
later, and being confined to the region adjoining the necrosis; this is 
especially the case after the 




Fig. 202.— Bacillary diphtheritis of the large intestine in 
dysentery (alcohol, gentian violet), a. Necrotic portion of 
the glandular layer of tlie mucosa, infiltrated with bacilli; b, 
intact inflamed mucosa; c, muscularis mucosae; d, sub- 
mucosa ; c, colonies of bacilli ; f, glands with living epithe- 
lium ; g, glands with necrotic epithelium and bacilli ; h, con- 
nective tissue infiltrated with cells ; «, blood-vessels. X 80. 



action of corrosive sub- ^ " 

stances, and high tempera- 
ture, and in ischsemia. In 
other cases, which belong 
chiefly to the infections, an 
inflammation is first estab- 
lished, the inflamed and 
infiltrated tissue later be- 
coming necrosed. In tuber- 
culous infections the ne- 
crosis occurs only after the 
tissue-proliferation has de- 
veloped and has existed for 
some time. 

N^ecrotic inflammations 
are most frequently seen on 
the mucous membranes, and 
are here usually called diph= 
theritis, particularly those 
which are caused by infec- 
tion. The necrosis may at 
first affect the epithelium, 
which in consequence loses 
its nuclei (Fig. 201, h) and 
later acquires a lumpy ap- 
pearance. If there are 

formed white, opaque patches upon the mucous membrane, as in the 
pharynx in diphtheria, the condition may be spoken of as epithelial or 
superficial diphtheritis. Usually, however, the designation diphtheritis is 

applied only to tis- 
^ *' sue necroses in 

which the infiamed 
and infiltrated con- 
nective tissue under- 
goes necrosis (Fig. 
202, a), and be- 
comes converted 
into a lumpy or 
granular mass with- 
out nuclei, or into 
a more homogene- 
ous mass contain- 
ing fibrin, in which 
the structure of the 
tissue can no longer 
be recognized. 
Diphtheritic 
^ sloughing of the 
tissues of a mucous 
' membrane is ob- 






Fig. 203.— Section of the uvula in pharyngeal diphtheria with croupo 
deposits (alcohol, aniline brown), a. Normal epithelium; ft, connective 
tissue of the mucous membrane ; c, reticulated fibrin ; f?, connective tissue 
of mucosa infiltrated with coagulated fibrin and round cells, and partly 
necrotic ; e, blood-vessels ; /, haemorrhage ; g, clumps of micrococci. X 75. 



340 



INFLAMMATION. 



served particularly often in the intestine (Fig. 202), but occurs also in 
other mucous membi'anes, as in those of the vagina, the descending uri- 
nary passages, and tlie region of the throat, where the tonsils are espe- 
cially frequently affected, etc. The necrotic tissue forms white, or 
grayish -white, or, through the admixture of blood or bile or other im- 
X3urities, dark green, yellow, brown, or otherwise colored sloughs, which 
are surrounded by reddened and inflamed tissue. If some time has 
already elapsed since its formation, and if a liquefaction of the tissue at 
the boundary between the living and dead tissues has occurred, with a 
separation of the latter, the necrosed i^arts form loosely attached or 
wholly free deposits lying on the surface of the membrane, these con- 
sisting at times only of small flakes, 
at other times of larger sloughs. 

Diphtheritis of mucous membranes 
may be associated with croupous de- 
posits (Fig. 203, c, d), so that the 
tissue-necrosis (fZ) may be covered 
over with fibrin (c). 

Wound-granulations may also ne- 
crose in the same way as do inflamed 
mucous membranes; such a condi- 
tion may therefore be called wowid- 
diplitlieritis. 

Acute tissue-necroses caused by 
infection occur in the case of the 
internal organs, chiefly in the lymph- 
glands (Fig. 204), spleen and bone- 
marrow, and are characterized by the formation of opaque grayish- 
white, j^ellowish, or dirty-gray sloughs. ISot infrequently fibrinous 
exudations are seen within the necrotic tissue (Figs. 203, d ; 204). 

In the necrosis caused by tuberculosis the destruction of the tissue 
occurs gradually, and bears the character of a caseation. 

When an inflammatory focus contains bacteria which excite putrid 
decomposition of albuminoid bodies, the inflammation may take on the 
character of a putrid gangrene ; and the tissue may disintegrate into a 
dirty gray or black, tinder- like mass which gradually dissolves and gives 
off an extremely disagreeable odor. Gas-bubbles are also sometimes 
developed in the focus. 

Literature. 

{Necrotic Inflammatiori.) 

Basch: Anat. ii. klin. Untersucliimgen iiber Diplitherie. Virch. Arch., 45 Bd., 1809. 
Cornil: Anat. patliol. des ulcerations intest. dans la dysenteric. Arch, dc phys., v., 
1883. 

Hartmann: Exper. Untcrsuchungen liber Chromsaurenephritis. Inaug.-Diss., Frei- 
burg, 1891. 

Hoffmann: Unters. liber, d. pathol.-anat. Verand. der Organe bei Abdominally phus, 
1869. 

V. Kahlden: Die Aetiologie u. Genese der acuten Nephritis. Beitr. v. Ziegler, xi., 
1892. 

Kaufmann: Die Sublimatvergiftiing, Breslau, 1888. Virch. Arch., 117 Bd., 1889. 
Kelsch: Contrib. a I'anat. patliol. de la dysenteric. Arch, de pliys., v., 1873. 
Lesser: Die anat. Verand. d. Verdaiiungskanales durch Aetzgitte. Virch. Arch., 83 
Bd., 1881. 

Letulle et Vaquez : Empoisonnement par I'acide chlorhydriqiie. Arch, de phys., i., 
1889. 




Fig. 204.— Diphtheritic ueerosis within a 
swollen mesenteric lympb-f?land, in typhoid 
fever (alcohol, flbrin-stain). Fibrin network 
between the necrotic cells. X 300. 



THE PROCESSES OF HEALING. 



341 



Marchand: Darin veranderungcn bei Tj^pbus abdomiualis. Cbl. f. allg. Path., i., 
1890. 

Matzenauer: Hospitalbrand. Arch. f. Derm., 55 Bd.. 1901. 
Neuberg-er: Wirkung des Sublimats auf die Nieren. Beitr. v. Ziegler, vi., 1889. 
See also §§ 90-93. 

II. The Termination of Acute Inflammation in Healing. 

§ 95. Should there occur in auy tissue whatsoever au acute inflamma- 
tion, sooner or later there always arise processes which have in aim the 
removal of the changes established and a restoration of the degenerated 
tissue, and which may therefore be regarded as processes of repair. If 
the cause which excited the inflammation is no longer present, these 
processes consist essentially in the cessation of the pathological exudation 
and its replacement by the normal vascular secretion, the removal or absorp- 
tion of the exudate p> resent and of the 7iecrotic tissue, and the restoration of the 
destroyed tissue. If the exciting cause of the inflammatio^i is still present in 
the tissue and active, it must be 7'emoved or rendered inert. 

The cessation of the alteration of the vessel=walls is brought about 
through the restoration of the normal blood-supi)ly to the damaged blood- 
vessels, so that the nutrition of the vessels again becomes normal. If the 
alteration was slight, and if the exciting cause of the inflammation had 
acted only for a short time — if it is the case, for example, only of the 
brief action of a trauma, or high temperature, or chemical substance, that 
was quickly removed — the restoration of the vessels may take place in a 
very short time, i. e. , in a time that may be measured in minutes and hours. 

When the exciting cause of the inflammation acts foi' some length of 
time — as, for example, in the case of bacteria which live and multiply in 
the tissues, or if changes are brought about through the inflammation 
itself, which act in such a manner as to alter the vessels — if there has 
been, for example, a tissue-necrosis — the vessels are subjected for some 
time to a continued harmful action, which hinders the complete restora- 
tion of their functions. 

The absorption of the exudate occurs in many cases easilj^ and 
quickly, in that it is taken up by the lymph-stream, eventually r.lso by 
the blood. This takes place most quickly in the case of serous exudates, 
yet in many places fibrinous exudates may also be quite rajiidly removed, 
but this occurs only when the coagula soon liquefy. Firmer fibrinous 
exudates, such as are formed especially upon the serous membranes, and 
also large collections of pus usually offer considerable resistance to ab- ^ 
sorption and are the cause of the prolonged course of the inflammation, ^ 
although the character of this may become changed from what it was in 
tli£— begi-iMiing. In very many cases absorption is accomplished by the 
simultaneous substitution, for the exudate, of embryonic tissue which 
later becomes changed into connective tissue. 

The sequestration and absorption of necrosed tissue, with the ex- 
ception of the casting- off of dead epithelium, which may be very quickly 
accomplished, always require a certain length of time, which varies 
according to the nature, situation, and extent of the necrosed tissue. In 
general, the inflammation persists as long as necrotic tissue is still pres- 
ent. Superficial necrosed tissues may be cast off after sequestration — that is, 
after the separation of the dead from the living tissues. In the case of 
deep-seated tissue-necroses in which the tissue does not soon undergo 
total liquefaction, absorption is usually slow, and is brought about 
through a gradual substitution of living tissue for the dead. 



3^2 



IXFLAMMATIOX. 



The regeneration of the degenerated tissue is depeudent, for its oc- 
currence, partly upon the degree aud extent of the degeueratiou, partly 
upon the nature of the tissue, and partly upon the mode of action of the 
agent exciting the inflammation. 

If the tissue-cells of the inflamed area are but slightly degenerated, 
they are quickly restored when the nutrition becomes normal. If single 
cells are lost but the organization of the whole is not disturbed, there can 
take place in most tissues a rapid renewal of cells through a regenerative 
growth of the remaining cells. This is true particularly of the different 
forms of connective tissue, the surface epithelium, liver- and kidnej - cells, 
while ganglion-cells, bone-cells, cartilage-cells, and heart-muscle cells 
possess but little or no power of regeneration (see Chapter YL). Ex- 
tensive destruction of tissue with solutions of continuity, wounds, frac- 
tures, supiDurations, necrotic inflammations, etc., lead to tissue-prolifer- 
ations, which are indeed sufficient to close the defect, but for the greater 
part do not lead to a restoration of the normal tissue, but to the forma- 
tion of a tissue of a lower grade, which in its earliest stages is known as 
granulation tissue, in its mature form as cicatricial tissue. Of the 
same character is also the tissue which in the course of time is substi- 
tuted for exudates and tissue -necroses that are absorbed with difficulty. 

A7ith the entrance of regenerative proliferation and the formation of 
granulation tissue, tliere appears in the course of the inflammation a 
phenomenon which later gives to the inflammation an especial charac- 
ter, so that it may be designated a proliferating inflammation. 

The phenomena of proliferation begin in inflamed tissues, at the 
earliest after eight hours, but are usually first clearly recognizable after 
from t went J' -four to forty-eight hours. 

In general, they appear the more rajDidly the milder the inflamma- 
tion and the more quickly the i^athological exudation is overcome/ or 
dimi>»^hed. Sui)j)uration, necrosis, and gangrene of the tissues hinder 
proliferafT^Trsuid retard the beginning of repair, or at least confine the 
reparative processes to the neighboring tissues. 

Every tissue capable of proliferation furnishes formative cells for 
tissue of its own kind or for one closely related to it. Pus-cori)uscles are 
not formed by the tissue-cells; on the other hand, cells neidi/ developed 
from tJie tissue-cells by proJifercdion way become mi.ved with the exudate, 
degenerate in the same, and die. Thus not all the cells newly developed 
through proliferation fulfil their function of producing new tissue. 

The removal of the exciting cause of inflammation takes -place very 
differently in different cases, and depends in the first place upon the 
nature of the cause. Many traumatisms and thermal influences act but 
for a short time, and have no further influence upon the course of the 
inflammation. Many substances acting chemically may be quickly taken 
up by the tissue-juices and made inert, or excreted, while others remain 
locally active for a longer time. Of the bacteria producing inflammation, 
many soon die, while others live and constantly produce new generations 
which in turn cause new inflammation, often in such a way that in the 
first diseased focus the inflammation may subside and healing take place, 
while in the neighborhood, or even in more distant regions, metastatic in- 
f animations develop. 

On account of the great differences which exist both in the nature and 
the behavior of the exciting cause of the inflammation, as well as in the 
course of the inflammatory tissue-degeneration and the exudation, and in 
the course of the healing processes, it is easy to understand that the whole 



THE INFLAMMATORY NEW- FORMATION OF TISSUE. 



343 



course of an iiiflamniatiou, even to its termination in healing, may vary 
greatly in different cases, so that all the possibilities of its course can 
hardly be reviewed. At the same time it is not difficult to comi)rehend 
the decline of the different forms of inflammation, since ultimately the 
whole process is always made up of the same factors — that is, of tissue- 
degeneration, pathological exudation, and of proliferative processes, the 
last of which are calculated to remove the disturbances caused by the 
first two factors. 

yeumann groups under the term inflammation all those phenomena -which develop 
locally after a primary tissue-lesion, and are directed toward the healing of this lesion. 
According to this view, regeneration is, tlierefore, the most important part of the in- 
flammatory process, in tliat it is especially adapted to restore the defect of tissue caused 
b}^ the primary tissue-lesion, or, as JSeuiuana puts it, to restore the uninterrupted con 
tinuity of the tissue. Such an identification of inflammation with regeneration I hold 
as inadmissible, in the first place because tissue-regenerations occur which clinically 
and anatomically in no w^ay bear the character of an inflammatory process. Then also 
the inflammatory pathological exudations cannot be regarded as phenomena that can 
be compared with regeneration, and that like it, have for an end the healing of the 
^jrimary tissue-lesion. Even if they act favorably in individual cases, this is not 
always true. Much more often do they cause serious damage which increases that 
established by the primary tissue-lesion, and often enough form a hindrance to the 
rapid enti-ance of the healing process. 

In ni}" opinion the tissue-proliferations do not form an essential part of inflamma- 
tion; the inflanmiation already exists before the}^ are established. Only in the late 
stages of inflammation do they form a part of the inflammatory process, and represent 
that part of the same which can bring about the healing. It is of no especial signifi- 
cance ^\•hether the processes of proliferation be regarded as a part of the later stages of 
inflammation or as a necessary sequela of the inflammatory tissue-degeneration, sepa- 
rated f j-om tlie inflammation in a narrow sense, and considered under the point of view 
• of tissue-repair. 

11. The Inflammatory New=formation of Tissue, Substitution of 
Exudates and Tissue=necroses by Connective Tissue. 

§ 96. The inflammatory proliferation of tissue is essentially a 
'regenerative process Avhich has for its aim the comx)ensation of the tissue - 
^ lesions produced by the causes of inflammation." Under especial condi- 
tions it leads not infrequently to a hjqjerplastic proliferation of connec- 
tissue, fi'ustiates its 'own aim, and causes new damage. This is 
particularly the case when, as the result of the persistence of the cause 
of the inflammation in the organism (chronic infection), or th^ persistence 
of the residue of the acute inflammation (exudate, abscess, tissue-necro- 
sis), there is kept up a permanent condition of inflammation. 

The inflammatory new-formations of tissue develop in essentially the 
same manner as the regenerative and hyperplastic tissue-proliferations 
described above (§§ 82-87). Thej^ are distinguished, however, from the 
simple regenerations by the fact that they are accompanied, at least dur- 
ing a part of their course, by disturbances of circulation and pathological 
exudations, and especially by an emigration of leucocytes, these factors 
exerting a modifying influence upon their course. 

The granulation tissue, which forms in the course of an inflamma- 
tion, is nothing moi'e than an embryonic tissue arising through cell= 
proliferation and infiltrated with leucocytes. Primarily it consists of 
cells and neidy formed vessels which at tirst depend for their support upon 
the ground- substance of the tissue from which they develop, but soon 
form for themselves a new ground-substance. 

The cells of the granulation tissue are partly proliferated tissue= 



INFLAMMATION. 



cells (Fig. 205, ?>, <?, d), and partly mono= and poly nuclear leucocytes 

(« aj. In the majority of cases the proliferated cells are connective- 
tissue cells, which later produce connective tissue (Fig. 205, d, e) and 




fully developed conuective tissue. \ .jIH.!. 

are, therefore, known as fibroblasts. Granulation tissue may contain 
also the offspring of other tissue — for example, of periosteal tissue, mar- 
row tissue, muscle tissue, or osteoblasts, cJwndroblasts, and sa)X'ohtasts, 
which are able to form bone, cartilage, and muscle tissue. There may 
also be found in the granulation tissue developing within glands neirJ}/ 
formed glandular ejyitheliiou, and in that developing in or upon mucous 
membranes or the integument, also newly formed corerhig epithelium : and 
these are able to produce epitltelial tissue-formations. The formative eells of 
granulation tissue may move away from the place of their origin, and are 
thus in a certain sense wanderinf/ eells. In the formation of connective 

tissue they take on the most varied shapes 
(Fig. 205, c, dy e). At times they form 
also polynuclear cells (e,). They are 
characterized b^' large, bright, oval nu- 
clei, which do not stain very deeply with 
nuclear stains, and are therefore dis- 
tinguished from the nuclei of leucocytes 
which stain very intensely. The forma- 
tive cells of the connective tissue are 
often termed epithelioid eells on account 
of their resemblance to epithelial cells. 

The leucocytes of granulation tissue 
are cells which have wandered from the 
blood-vessels, and from their presence it 
may be concluded that the inliammatory exudation from the vessels still 
continues. Their number may in general be regarded as an index of 
the degree of the still existing inflammation complicating the recovery. 




Fig. 2U6.— Cross-section of blood-vessel 
fi-om the deep layers of the skin, forty hours 
after painting the skin of a rabbit with 
tincture of iodine (Flemming's soUUion, 
safrauin). o. Endothelial cells with mi- 
toses: 7), leucocytes. X 350. 



GRANULATION TISSUE. 



345 



The blood=vesseIs of granuSation tissue develop by offshoots from 
old vessels (see Fig. 160), which very soon, indeed at the time in which 
the emigration of leucocytes occurs (Fig. 206, J)^) give evidence of pro- 
liferative processes («) ; and in the formation of granulation tissue they 
take ou a very active growth. The j^oung embryonic tissue is conse- 
quently very richly supplied with vessels, which give to it a red appear- 
ance. At the time of the transformation of granulation tissue into 
connective tissue or scar tissue, 
an obliteration of the vessels oc- 
curs, and the cicatrix conse- 
quently becomes pale. 

If upon any part of the body- 
surface there occurs an open 
wound, which does uot become 
infected with bacteria or seri- 
ously injured in any way, the 
edges and base of the wound 
after twenty-four hours become 
deep-red and somewhat swollen. 
The individual constituents of 
the tissue can still be clearly 
recognized, only the tissue ap- 
peals somewhat swollen, and 
here and there small shreds of 
necrotic tissue may be seen. On 
the second day the gelatinous 
condition of the tissues is more 
apparent, the outlines of the 
individual tissue -elements are 
effaced, and the color becomes 
grayish -red. On the wound 
there lies a reddish-yellow fluid. 
From the second clay on there 
appear over the whole wound 
small red papules, which rap- 
idly increase in number and 
size, become confluent, and after 
two to three days form a granu- 
lar red surface — a granulation 
surface. This is covered with a more or less abundant wound-secre- 
tion, which forms a gray, gelatinous layer, later becoming more yel- 
low and creamy. This layer consists of a coagulahle exudate rich in 
albumin and numerous round cells which usually possess lobulated or 
pigmented nuclei and are designated ^?(s-co>2>i<sd^5, and which, being in- 
capable of further development, undergo disintegration. 

The changes which the surface of the wound shows are in the first 
two days dependent upon the local hyperaemia and the infiltration of the 
tissue with cellular and fluid exudate, and upon the swelling and lique- 
faction of the tissue ; after this time there is added thereto a tissue-pro- 
liferation ^nth new-formation of vessels, leading to the development of 
wound=granulations. After a few days there will have developed in 
the wound a granulation tissue (Fig. 207, a) consisting of fibroblasts aiid leuco- 
cytes, and rich in wide vessels (c), and in which there very soon appears a 
fibrillar groimd- substance. The leucocytes, which belong chiefly to the 




Fig. 207,— Wound-granulations from an open wound 
with flbrinopurulent covering (Miiller's fluid, htematoxy- 
lin). a. Granulation tissue ; b, flbrinopurulent layer ; c, 
blood-vessels. X 135. 



346 



INFLAMMATION. 



polyiiiiclear form, are found in all the layers of the skin in fresh granula- 
tions, but heap themselves particularly in the superficial strata, and, 
embedded in fibrin, cover over the surface of the granulation tissue [h). 

The freshly formed fibroblasts are round cells ; later there develop 
cells partly club-shaped, partly spindle-shaped, partly with many 
branched processes (Fig. 205, c, d), which in various ways unite the 
cells. At the same time the number of the large formative cells in- 
creases, so that they finally surpass the small round cells in number, and 
in places come to lie closely together. When their number has reached 
a certain point, the development of connective tissue begins — i.e., the 
formation of the fibrillar intercellular substance (Figs. 205, d, e; 207, «) 
— which is completed in the manner described in § 84. When a certain 
degree of fibrillse-formation has been reached the process conies to a 
standstill, the remains of the fibroblasts with their nuclei remain as fixed 
connective-tissue cells (Fig. 205, e), continue to live, and attach them- 
selves to the surface of the bundles of fibrillae. The process has then 
reached its termination — the granulation tissue has become scar tissue. 

In open wounds of the skin, when infection does not disturb the 
course of healing, the formation of granulation tissue lasts until the 
wound is again covered with epithelium. The regeneration of the latter 
proceeds from the edges, the epithelium gradually pushing itself over the 
granulations. With the formation of connective tissue the reproductive 
processes essentially terminate, but transformation processes continue in 
the cicatricial tissue for some length of time. Shortly after its formation 
the cicatrix is rich in blood and appears red ; later it loses a portion of 
its vessels through their obliteration, becomes pale, and contracts to a 
volume much less than the original. Large scars of the skin show per- 
manently a smooth surface, since the papillary bodies are not again 
formed or only imperfectly (Fig. 209, e). The tissue of the scar remains 
for several months abnormally rich in cells, but in the coui'se of time 
becomes poorer in cells and harder, and comes to contain elastic fibres. 

When the healing of a wound occurs in such a manner that the tissue - 
defect is closed by the formation of a granulation tissue visible to the 
narked eye, the process is designated repair by second intention {])er secun- 
dam intention em). 

The healing of incised wounds of the skin, tvhose edges, united by 
sutures, grow together by first intention, takes place in essentially the same 
manner as the healing of an open wound by second intention ; but the 
fjrocesses of inflammation, proliferation, and new -formation of tissue are 
less prominent, partly because they take place below the skin, and partly 
because they are of much less extent and intensity. 

The result of such a cut is always a more or less abundant exudation 
on the surfaces of the wound, forming a coagulated mass often contain- 
ing blood (Fig. 208, c), which glues together the opposing wound-sur- 
faces. Very soon there arises an inflammatory infiltration of the edges 
of the wound, which varies greatly in different cases, and when the course 
of repair is aseptic never reaches any significant degree (g, h), attaining 
its maximum in from two to four days, diminishing from the fifth to the 
seventh day, and completely disappearing at or soon after the end of 
the second week. The inflammatory infiltration is usually greater in the 
neighborhood of the wound-sutures than at the edges of the wound. 

As early as the second day regenerative processes of proliferation 
begin in the connective tissue and in the vessels, and lead, in the course 
of several days, to the formation of an embryonic tissue, which lies partly 



HEALING BY FIRST INTENTION. 



347 



in the spaces of the connective tissue at the edges of the wound (Fig. 
208, /), and partly extending into the open space of the wound itself (/) ; 
and here gradually grows into the coagulum which is present and replaces 
it. This tissue is usually present in varying quantity in different parts 
of the wound (Fig. 208), and may be entirely absent in places. After a 
certain number of days, the time varying according to the size of the 




Fig. 208.— Healing of incised wound of skin united by suture (Flernming's solution, safranin). Prepar- 
ation made on the sixth day. a. Epidermis ; b, corium ; c, fibrinous exudate, in part huemorrhag-ic ; d, 
newly formed epidermis, containing numerous division-figures, and with plugs of epithelium extending 
into the underlying exudate ; e, division-figures in epithelium at a distance from the cut ; /, proliferating 
embryonic tissue, developing from the connective-tissue spaces, and containing cells with nuclear division- 
figures, and in part also vessels with proliferating walls ; g, proliferating embryonic tissue with leucocytes ; 
h, focus of leucocytes in deepest angle of wound; i, fibroblasts lying within the exudate, one showing a 
nuclear division-figure ; k, sebaceous-gland ; Z, sweat-gland. X 70. 

wound, the thickness of the exudate between the edges of the wound, and 
the intensity of the proliferation, the masses of embryonic tissue growing 
from the edges of the wound blend together, and there follows the forma- 
tion of young connective tissue, which joins the edges of the wound to- 
gether, and at the same time extends also into the old tissue, so that the 
boundary between the old and the new tissue becomes indistinct. 

While connective tissue is being formed in the deeper parts of the 
wound, the epithelial covering on the surface is also being regenerated 
(Fig. 208), and indeed in this manner, that the epithelium pushes over 
the wound-surface, and through a continuous cell-division (d, e) forms 
an epithelial covering consisting of many layers. The epithelium may 



34:8 



INFLAMMATION. 



push across the wound-surf ace even before a new-formation of cells has 
taken place. 

The young connective tissue of the scar uniting the edges of the 
wound is distinguishable for a long time from the neighboring older tis- 
sue through its richness in cells (Fig. 209, f), as well as through the 
finer fibrillation of its ground-substance ; and in large incised wounds 
of the skin there may be found in it, here and there, after the lapse of 




X 



Fig. 2U9.— Cutaneous portion of a laparotomy cicatrix, sixteen days after the operation (Miiller's 
fluid, haematoxylin. Van Gieson's). ft. Epithelium; h, corium; c, subcutaneous fat tissue; d, scar in 
corium ; e, new epithelial covering ; /, scar in fat tissue. X 38. 

weeks or even months, slight evidence of proliferation and inflammations. 
In general, however, transformation processes gradually occur in the 
blanching scar, so that its tissues come to approach more closely to the 
normal, and finally the place of the incision can no longer be easily rec- 
ognized. If the wound heals by the interposition of abundant embryonic 
tissue, there may occur a defect of the papillary bodies (Fig. 209, e), so 
that the scar remains smooth. 

§ 97. When there is found upon the surface of an inflamed serous 
membrane (Fig. 210, a) an adherent layer of fibrin (h), there usually 
develop quickly beneath it granulation=formations. The earliest begin- 
nings of these can be seen as soon as the fourth day after the formation 
of the fibrinous deposit, and they consist at first of the appearance of 
fibroblasts (/) in the deepest layers of the fibrinous membrane. These 
arise through the proliferation of the connective-tissue cells of the af- 
fected serous membrane, and wander to the surface, and into the fibrin. 
In association with this phenomenon there follows very soon a new-f orma- 



ORGANIZATION OF FIBRINOUS EXUDATES. 



349 



tion of blood-vessels, and in the coni'se of days or of we^ks there is 
develoi)ed upon the surface a vascular embryonic tissue or granulation 
tissue, which, when the overlying fibrin layer is very compact, lifts this 
up in toto (Fig. 211, 

h, c) ; but, in the case y f 

of fibrin possessins: a /^''^ / i^w^^^^ 

looser network, pene- ^ ~ f ^ . w ^-t-^^ 

trates into the inter- 
stices of the fibrin- 
membrane (Figs. 210, 
/; 212, b, d), and in 
the course of time re- 
places the fibrin. Re- 
mains of the fibrin 
(Fig. 212, c) may, 
however, often persist 
for a long time, weeks 
or months, within the 
granulation tissue. 

In the formation 
of the granulation 
tissue and the devel- 
opment of scar- tissue 
the epithelium (endothelium) of 
since it produces no fibroblasts. 




Fig. 210.— Fibrin deposit and beginning formation of granulation 
tissue in a fibrinous pericarditis five days old (Miiller's fluid, hieiiia- 
toxylln). a, Epicardium; h. flbrin-menibraue ; t\ dilated, congested 
vessels ; r/, round cells inflltratijig the tissue ; e, Ivuiph-vessel filled with 
cells and clots ; f, fibroblasts within the deposit. X 150. 



the serous membranes takes no part, 
On the other hand, the products of 
the inflammatory proliferation become covered later with epithelium. 

The final result of tlie process is tlie formation of connective tissue, 
which leads either to a thickening of the serosa which had been covei ed 

with fibrin, or to an adlip- 
sion of the opposing surfaces 
of the serous membrane, so 
that the inflammation may 
be designated as adhesive. 
The result in individual 
cases depends partly ui^on 
the amount of the fibrin 
deposit and partly upon 
the situation of the affect- 
ed organ, and its condition 
during the process of heal- 
ing. 

Small deposits of 
fibrin, limited to one sur- 
face of the serous mem- 
brane, lead only to thick- 
enings of the serosa, 
which, becoming pale with 
the obliteration of the ves- 
sels, are represented final- 
ly by white thickenings 
frequently designated as 
tendinous spots. The 
firm glueing together of two serous layers by an abundant deposit of fibrin 
leads also to a firm adhesion of the same through the abundant forma- 




FiG, 211.— Development of granulation tissue in the pleura, in 
bronchopneumonia and pleuritis of fourteen days' duration (alco- 
hol, Yan Gieson). a, Hvperaemic, infiltrated pleura; i», very vas- 
cular granulation tissue; c, fibrin; d, pus-corpuscles, and gran- 
ules of precipitated albumin. X 100. 



350 



INFLAMMATION. 




Fig. 212.— Formation of granulation tissue In the fibrinous 
deposits of a pericarditis several weeks old (Miiller's fluid, 
tiaematoxylin, eosin). a, Epicardium ; b, deposit on the epi- 
cardiuin.- consisting of granulation tissue (d), and fibrin (c). 
X 40. 



tion of connective tissue. In 
the case of a smaller amount 
of fibrin, and repeated rub- 
bing of the membranes upon 
each other, there develop 
only loose memhranous or 
stringy adhesions, which still 
j)ermit the serous surfaces 
to move upon one another. 
Yery large amounts of fibrin 
may also, under certain con- 
ditions, in part permanently 
resist absorjition, so that 
they remain lying within the 
newly formed connective 
tissue, and then usually be- 
come calcified. 

Coagulated exudates in 
the lungs may quickly be- 
come liquefied and absorbed, 
but it also happens that 
their removal may be asso- 
ciated with a connective- 
tissue proliferation, which 
leads to an induration of the 
lung. The proliferation pro- 
ceeding from the lung tissue 
leads either to a thickening 
b) or extends into the exudate lying in the 

which later comes to 




of the septa (Fig. 213, a 

alveoli, in the form of an embryonic tissue (d, e) 
contain newly formed blood- 
vessels {g). 

riasses of coagula with= 
in blood=vessels, which are 
called thrombi, give rise, in 
case no infection occurs, to 
an inflammatory — that is, 
associated with cell -emigra- 
tion — proliferation of the 
vessel -wall, a proliferating 
vasculitis. This process cor- 
responds exactly to the in- 
flammatory proliferation of 
the serous membranes. It 
is entirely immaterial 
whether the thrombosis has 
been caused by a preceding 
inflammatory process or by 
any other conditions, inas- 
much as the presence of the 
mass of coagulum is sufh- 
cient to cause inflammation 
and tissue -proliferation. 

The first change intro- 



I V 



— e 



^^^^^^ 

^^^^^ 

Fig. 213.— Intraseptal and intra-alveolar formation of con- 
nective tissue in the lung (alcohol, haematoxylin). a. Thick- 
ened flbrocellular alveolar septum, in part infiltrated with 
round cells (&); c, flbrlnocellular exudate in the alveoli; 
d, intra-alveolar formative cells; e, strand of spindle-cell 
fibroblasts; g, intra-alveolar nev^^Iy formed blood-vessel. 
X 200. 



ORGANIZATION OF THROMBI. 



351 



duced in the substi= 
tution of thethrom= 
bus by connective 
tissue is here also 
the appearance of 
fibroUasts (Fig. 214, 
h), which arise from 
the vessel-wall, and 
later, with the aid of 
vessels growing in 
from the vessel -wall 
and its neighbor- 
hood, form an em- 
bryonic tissue, which 
ultimately changes 
into connective tis- 
sue. The complete 
substitution of an 
obturating throm- 
bus or embolus 
leads to the obliter- 
ation of the vessel - 
lumen by vascular- 
ized connective 
tissue (Fig. 216, g) ; 
the substitution of a parietal thrombus, on the other hand, results in the 
formation of fibrous thickenings of the vessel-wall. As the result of an 




Fig. 315— Border of a recent haemorrhaffic infarct of the lunff (Miiller's fluid, hgematoxylin, eosin). a. 
Alveolar septa without nuclei, whose capillaries are filled with hyaline thrombi ; J>, septa, containing 
nuclei; c, vessels with red thrombi; d, dj, alveoli filled with coaeulated blood; e, fibrinocellular exudate 
in the alveoli. X SW). 



imperfect substitution and liquefaction of the part not substituted, there 
arise strands and threads of connective tissue, which cross the lumen of 
the vessel. The calcification of portions of thrombi not substituted by 
20 





Fig. 314— Development of embryonic tissue in a thrombosed femoral 
artery of an old man, three weeks after ligation (alcohol, hasmatoxj'lin). 
a. Media ; h, elastic limiting membrane ; c, intima, thickened through 
older inflammatory processes : f/, coagulated blood ; e, cellular infiltration 
of the media, /, of the intima ; g, round cells, partly in the thrombus, 
partly between it and the intima; /i, different forms of formative cells. 
X 300. 



352 



INFLAMMATION. 



connective tissue leads to the formation of vessel-stones (arterio- or 
phleboliths). 

Necrotic tissue, which cannot be sequestrated and discharged exter- 
nally, is also replaced by a vascular connective tissue, which becomes 
converted into scar tissue ; and this substitution takes place in the same 
manner as in the case of fibrinous exudates and thrombi. The requisite 
condition for this substitution is that the necrotic tissue shall contain no 
substances (bacteria) which hinder tissue-proliferation or excite severe 
inflammation. In general it is immaterial how the necrosis has occurred, 
and whether the necrotic tissue is free from exudate or is infiltrated with 
exudate or blood (Fig. 215, d, dj. The first phenomenon leading to 
healing is the association with the inflammatory exudate (e), in the 
neighborhood of the necrosis, of a tissue-proliferation, which produces 
granulation tissue, which grows toward the necrotic tissue (Fig. 216, 
d, e), dissolves it, and finally replaces it. If this process is not disturbed 
by any influence whatever, even very large tissue-necroses may in the 
course of weeks and months be made to disappear and may be replaced 
by connective tissue. It may also happen, however, that certain tissues 
resist absorption, or that the development of granulation tissue stops so 
early that remains of the necrosed tissues persist and later become calcified. 

When, as the result of an inflammation or ischsemia within an organ, 
only the more sensitive elements die — for example, epithelial or muscle 
cells — while the connective tissue remains intact, the absorption of the 



o e f) (1 c f 




Fig. 216.— Periphery of a healing pulmonary infarct (Miiller's fluid, haematoxylin, eosin). a, Blood- 
extravasate changed into a yellowish granular mass ; b, necrotic alveolar septa without nuclei ; c, newly 
formed connective tissue ; d, vascular granulation tissue within the alveoli ; e, fibroblasts within alveoli 
containing the residue of the hsemorrhage ; /, artery ; g, vascular connective tissue formed within the 
artery at the place of the embolus. X 40. 



necrotic portions takes place very quickly, and there is formed within a 
short time a scar or callus of connective tissue (Fig. 217, e), in which the 
specific tissue -elements are lacking. 

Pus is quickly absorbed from small abscesses, and the defect closed by 



HEALING OF ABSCESSES AND EMPYEMATA. 



353 




granulation and scar tissue. Large amounts of pus may be absorbed from 
the body -cavities and from the lungs. 

Abscesses cause in their neighborhood a proliferation of granula= 
tion tissue which leads to the formation of an abscess=membrane. The 
abscess- cavity may become obliterated through the absorption of the pus 
and the growing to- 
gether of the granu- 
1 a t i o n - membrane 
covering the walls 
of the cavity; the 
abscess finally heals 
and leaves a scar. 
Incomplete absorp- 
tion may lead to 
thickening of the 
pus and later a calci- 
fication of the resi- 
due. If the pus does 
not become inspis- 
sated, the abscess 
may persist and in 
the course of time 
may be increased in 
size by secretion 
from its walls. 

Empyemata 
may heal in a similar 
manner to abscesses 
through absorption 
of the pus. At the 
time of absorption 
the tissues enclosing 
the pus produce 
granulation and 

scar tissue, which may reach a considerable size when the process of 
absorption takes a long time (Fig. 223). When incompletely absorbed, 
calcification of the thicJcened pus may occur. 

Foreign bodies, so far as they are absorbable and exert no specific 
influence upon their surroundings, are likewise dissolved, and replaced 
by connective tissue in the same way as are tissue-necroses or fibrin 
masses. If they possess accessible interstices, these may be penetrated 
by granulation tissue. If their mass cannot be absorbed, they become 
encapsulated (Fig. 217). 




:0> 




Fig. 217.— Fibroid area in heart-muscle. Section through a muscle-tra- 
becula which has undergone fibroid change (Muller's tluid, haeinatoxylin), 
a, Endocardium; h, cross-section of normal muscle-cells.; c, hyperplastic 
connective tissue rich in cells ; d, atrophic muscle-cells in hyperplastic 
connective tissue ; e, dense connective tissue, poor in nuclei and contain- 
ing no muscle-cells; f, vein, in whose neighborhood muscle-cells are 
still preserved ; g, small blood-vessels ; 7?, small-celled infiltration. X 40. 



The role played in the course of inflammation by the leucocytes which emigrate 
from the blood=vessels has not yet been satisfactorily explained. It is certain that 
the polynuclear leucocytes undergo no progressive changes, but either wander farther 
or die, and in part are taken up and destroyed by the fibroblasts (see § 98). The fate 
of the mononuclear leucocytes, particularly of the larger forms, is not definitely known. 
By the majority of authors it is assumed that they also take no part in the development 
of connective tissue, and that there is no ha?matogenous formation of connective tissue. 
It is, however, to be noted that many authors {Arnold, Metschnikoff, Schottldnder, Krom- 
pecher) hold that emigrated leucocytes may become transformed into fibroblasts. The 
basis of this difference of opinion rests upon the fact that the cells in question — round 
fibroblasts and mononuclear leucocytes — are very similar to each other, and forms often 
appear whose origin cannot be -definitely determined. Therefore it cannot be said with 



354 



INFLAMMATION. 



certainty whether the so-called small=celled infiltration— that is, the collection of 
mononuclear round cells in the tissue — which is so frequently seen in inflammation, is 
of haematogenous origin, or Avhether in part it is made up of proliferated tissue-cells. 
Rihhert believes that there is reason for regarding these collections of cells as lymph- 
nodes. 

Recently there have been differentiated among the cells of the perivascular foci 
especial forms, as plasnia=cells {Unna) or Krwnelzellen''^ {wn Marschalko). These 
are mononuclear, round or oval, occasionally also long cells {von Marschalko, Krom- 
pecher) which stain deeply with methylene-blue, and, as a result of the close clumping 
of the protoplasm at the periphery of the cell, show a light area around the nucleus 
which is usually excentrically placed and is furnished with a chromatin-network and 
five to eight chromatin granules. Unna, who first described these cells, regarded them 
as offspring of the connective tissue which die. On the other hand, wn Marschalko, 
Schottldnder, Krompecher, and Justi regard them as offspring of leucoc3'-tes, and it is 
probable that their view is the correct one. Von Marschalko regards it as probable that 
they produce connective tissue ; Schottldnder and Krompecher are convinced that they 
become changed into fibroblasts and can form connective tissue. Plasma-cells, therefore, 
represent transition stages between the haematogenous wandering-cells and connective-tissue 
cells. 

According to the investigations made up to the present time, it is not possible to 
make positive statements regarding the significance and fate of the emigrating ha3ma- 
togenous wandering-cells. The possibility that they are able to form connective-tissue 
cells is conceded, but is not a proved fact. It is also possible that among the emigrat- 
ing leucocytes there are cells arising from proliferating endothelium of the blood- 
vessels, or that young motile connective-tissue cells wander into the vessels and then 
again pass out, and that the last two named are able to form connective tissue. For 
the solution of these problems we must look to new investigations. 



Literature. 

{Inflammatory Proliferation of Tissue.) 

Anschiitz: Primarer Wundverschluss. Beitr. v. Bruns, xxv., 1899. 

Arnold: Theilungsvorgange an den Wanderzellen. Arch. f. mikr. Anat., xxx., 1887; 
Altes u. ISIeues iiber Wanderzellen. Virch. Arch., 132 Bd., 1893; Die Geschicke 
der Leukocyten in der Fremdkorperembolie. lb., 133 Bd., 1893. 

Ballance: The Genesis of Scar Tissue. Verb. d. X. internat. med. Congr., ii., Berlin, 
1891. ^ 

Baquis: Et. exper. sur les retinites. Beitr. v. Ziegler, iv., 1888. 

Bardenheuer : Die histologischen Vorgauge bei der durch Terpentin hervorgerufenen 
Entziindung im Unterhautzellgewebe. Beitr. v. Ziegler, x., 1891. 

Baumg-arten : Die sog. Organisation des Thrombus, Leipzig, 1877 ; Die Rolle der fixen 
Zellen iu der EntzUndung. Berl. klin. Woch., 1900. 

Beneke: Die Ursachen der Thrombusorgaaisation. Beitr. v. Ziegler, vii., 1890. 

Borst: Chron. Entziind. u. pathol. Organisation. Ergeb. d. allg. Path., iv., 1900. 

Biittner: Verb. d. Peritonealepithels bei Entzundung. Beitr. v. Ziegler, xxv., 1899. 

Busse: Heilung asept. Schmittwunden d. Haut. Virch. Arch., 134 Bd., 1893. 

Cassaet: De I'absorption des corps solides. Arch, de med. exp., iv., 1892. 

CMamsky: Methoden der Darmvereinigung. Beitr. v. Bruns, xxv., 1899. 

Coen: Veranderung d. Haut unter d. Wirkung von Jodtinctur. Beitr. v. Ziegler, ii., 
1888. 

Cornil: Des hematomes. Arch, des sc. med., Paris, 1896; Adherences des membranes 

sereuses. Arch, de med. exp., 1897. 
Cornil et Carnot: Regen. cicafricielle des conduits et des cavitse muqueuses. Arch. 

de med. exp., 1898 and 1890; Cicatrisation des plaies du foie. Sem. med., 1898. 
Councilman: Acute Interstitial Nephritis (Plasma-Cells). Jour, of Exp. Med., 1898. 
Eberth.: Kern- u. Zelltheilung bei Entzundung. Festschr. f. Virchow, ii., Berlin, 

1891. 

Fischer: Experim. Unters. lib. d. Heilung v. Schnittwunden d. Haut. Inaug.-Diss., 

Tubingen, 1888. , 
Foa: Ueber Niereninfarkte. Beitr. v. Ziegler, v., 1889. 

Giovannini: Lesioni inflammatorie e neoplastiche della pelle. Arch, per le Sc. Med., 
X., 1886. 

Graser : Die feineren Yorgange bei Verwachsung peritonealer Blatter. Deut. Zeit. f . 
Chir., xxvii., 1888; Zusammenheilung von serosen Hauten. Verh. d. Chir. -Congr., 
1895. 

Grawitz: Wanderzellenbildung in der Hornhaut, Virch. Arch., 158 Bd., 1899. 



INFLAMMATORY PROLIFERATION OF TISSUE. 



355 



Hallwachs: Ueber Einheilen von organischem Material. Langenbeck's Arch., 24 Bd., 
1879. 

Hamilton: On Sponge Grafting. Edinburgh Med. Jour., xxvii., 1881-82. 
Haug- : Ueber die Organisationsf ahigkeit der Schalenhaut des Hilhnereies, Miinchen, 
1889. 

Herbert: The Young Plasma-Cell in Chronic Inflammation. Jour, of Path., vii., 
1900. 

van Heukelom : Sarkome u. plastische Entziindung. Virch. Arch., 107 Bd., 1887. 
Hinsberg: Betheil. d. Peritonealepithels bei Einheilung v. Fremdkorp. Virch. Arch., 
159 Bd., 1898. 

Jacobsthal: Histologic der Arteriennaht. Beitr. v. Bruns, xxvii., 1900. 
Justi: Die Unna'schen Plasmazellen. Virch. Arch., 150 Bd., 1897. 
Karg: Entziindung und Regeneration. Dtsch. Zeitschr. f. Chir., xxv., 1887. 
Kiener et Duclert: Formation et guerison des absces. Arch, de med. exp., v., 1893. 
Klemensiewicz : Bau und Thatigkeit der Eiterzellen, Mitth. d. Ver. d. Aertze v. 
Steiermark, 1898. 

Krafft: Zur Histogenese des periostalen Callus. Beitr. v. Ziegler, i., Jena, 1886. 

Krompecher : Plasmazellen. Beitr. v. Ziegler, xxiv., 1898. 

Kriickmann : Heilung v. Lederhautwunden. v. Graefe's Arch., 42 Bd., 1896. 

Kiister: Wunden. Eulenburg's Realencyklop., xxvi. , 1901. 

Lejars: Sections. Traite de path, gen., i., Paris, 1895. 

March.and, F.: Einheilung von Fremdkorpern. Beitr. v. Ziegler, iv., 1888; Betheil- 
igung d. Leukocyten an d. Gewebsneubildung. Verh. d. X. internat. med. Congr., 
ii., Berlin, 1891. 

Marschalkd: Die Plasmazellen. Arch. f. Derm., 30 Bd., 1895; Cbl. f. allg. Path., x., 
1899. 

Marwedel: Verand. d. Knochenmarks bei Gewebsneubildung. Beitr. v. Ziegler, 
xxiii., 1898. 

Muscatello: Condiz. necess. alia produz. di aderenze periton. Arch, per le Sc. Med., 
XX., 1896. 

NikiforofF: Bau u. Entwickelungsgesch. d. Granulationsgewebes. Beitr. v. Ziegler, 
viii., 1890. 

Ostry: Karyokinesen in entziindlichen Neubildungen der Haut. Zeit. f. Heilk., iv., 
1883. 

Podwyssozki: Ueber die Regeneration der Driisengewebe. Beitr. v. Ziegler, i. and 
ii., 1884-87. 

Pogg-i- La cicatrisation immediate des blessures de I'estomac. lb., iv., Jena, 1888. 
Ranvier: Mecanisme hist, de la cicatrisation. Lab. d'hist. du College de France, 1900. 
E-einke: Proliferation u. Weiterentwickelung der Leukocyten. Beitr. v. Ziegler, v., 
1889. 

Ribbert: Das patholog. Wachsthum d. Gewebe, Bonn, 1896; Beitr. z. Entziindung. 

Virch. Arch., 150 Bd., 1897 
Roloif: Rolle d. Pleuroperitonealepithels bei d. Entsteh. d. Bindegewebsadhasionen. 

Arb. a. d. Inst. v. Baumgarten, ii., 1897. 
Salzer: Ueber Einheilung von Fremdkorpern, Wien, 1890. 

Scheltema: Veriinderungen im Unterhautbindcgewebe bei Entzimdung. Deut. med. 
Woch., 1886. 

Schottlander : Kern- u. Zelltheilung im Endothel d. entzund. Hornhaut. Arch. f. 

mikr. Anat., xxxi., 1888; Ueber Einsticlistuberkulose, Jena, 1897. 
Schujeninoff: Veranderungen d. Haut nach Aetzungen. Beitr. v. Ziegler, xxi., 1897. 
Senftleben: Verschluss der Gefasse nach der Unterbindung. Virch. Arch., 77 Bd., 

1879. 

Sh-erring-ton u. Ballance: Entstehung d. Narbengewebes. Cbl. f. allg. Path., i., 
1890. 

Tillmanns: Exp. u. anat. Unters. iiber Wunden der Leber u. Niere. Virch. Arch., 
78 Bd., 1879. 

Vermorel: Rech. sur I'inflamm. pleurale, Paris, 1898. 

Ziegler: Exper. Unters. liber die Herkunft der Tuberkelelemente, Wurzburg, 1875; 
Unl^ers. ilber pathologisclie Bindegewebs- u. Gefassneubildung, Wurzburg, 1876; 
Bethieligung der Leukocyten an der Gewebsneubildung. Verh. d. X. internat. 
med. Congr., ii., Berlin, i891; Die Ursachen der pathologischen Gewebsneubil- 
dungen. Festschr f. Virchow, ii., Berlin, 1891; Historisches u. Kritisches liber die 
Lehre von der Entziindung. Beitr. v. Ziegler, xii., 1892; Eutzundung. Eulen- 
burg's Realencykl., 1894; Entziindung der serosen Haute. Beitr. v. Ziegler, xxi., 
1897. 

See also §§ 90 and 98. 



356 



INFLAMMATION, 



IV. Phagocytosis Occurring in the Course of Inflammations, and 
the Formation of Foreign=body Qiant=ceIIs. 

§ 98. The presence in the tissues of the human body of small foreign 
bodies or of dead tissue-elements and tissue=detritus leads very often 
to a marked collection of cells about the embedded substance. At first 
these cells are leucocytes which have wandered out from the vessels, but 
later j)roliferating tissue-cells which have become motile wander into the 
neighborhood of the foreign body or dead tissue-remains. 

According to investigations by Leber, Buchner, Massart, Bordet, 
Gabritschewsky, and others, it is certain that the collecting of the cells 
is in part due to chemotaxis—i.e., by an attraction exerted by substances 




Fig. 318.— Granular cells In a focus of degeneration in the brain (teased preparation treated with osmic 
acid), a, Blood-vessel with blood; b, media; c, adventitia with lymph-sheath; d, unchanged gUa-cells; 
e, fatty glia-cells; /, glia-cells with two nuclei; g, sclerotic tissue; h, round-cells; hi-, round-cells with few 
fat-droplets ; /i2, fat-droplet spherules ; h^, pigment-granule spherules. X 300. 

which have been dissolved out of the foreign body or the tissue-detritus ; 
but without doubt other factors may determine the place where the cells 
collect. 

If the material while still undissolved comes within the neighborhood 
of the motile cells, it is very often taken up by the latter, and there 
occurs that phenomenon which is known as phagocytosis. If the proc- 
ess be observed under the microscope — as may very easily be done by 
mixing the richly cellular tissue-lymph of the frog with granules of soot 
— one sees that the mobile cells pour their protoplasm around the foreign 
bodies and through the union of the pseudopodia extended over the bod- 
ies receive them wholly into their protoplasm. Among the foreign 
bodies which penetrate from without are particularly the different /orms 
of dust (especially soot) which are taken into the lungs with the inspired 



PHAGOCYTOSIS. 357 

air, also bacteria which are very frequently taken up by leucocytes or by 
tissue-cells. It is to be noted, however, that a phagocytosis of bacteria 
does not occur in all infections, but is rather confined to especial infec- 
tions, and even in these does not occur 
in all stages of the local disease. 

Of tissue -detritus there occur most 
frequently fat- drojMs (Fig. 218, h^, hj, 
and disintegration - products of red 
blood-cells (h,), and these maybe taken 
up in such abundance by the cells that 
the latter may become entirely filled 
with them and become changed into 
large spherical forms, which have been 
designated /erf- ^/mw^^Ze cells and pigment- 
granule spherules. Besides fat and 
blood-pigment other tissue-elements — 
as, for example, fragments of the con- 
tractile substance of muscle, or of elastic fibres, or of fibrin — are taken 
up by cells. The cells which take up such substances are chiefly pro- 
liferating tissue-cells — fibroblasts, osteoblasts, sarcoblasts, etc. If an 
inflammatory exudation runs its course at the same time, and if the pro- 
liferating tissue contains leucocytes, they may also be talcen up by the phago- 
cytes (Fig. 219, a, b, c). 

Phagocytosis is a vital phenomenon of the cells which iDrimarily has 
for its aim the taking=up of food ; and it cannot be doubted that in in- 
flammatory foci this aim is in part fulfilled. This is particularly the 
case in the taking-up of leucocytes by fibroblasts, sarcoblasts, etc. ; one 
can at least see clearly how the leucocytes (Fig. 219, a, b) within the 
cells undergo a progressive disintegration (c, d, e) and finally are wholly 
destroyed. How far other corpuscular elements serve as food-material 
is dependent upon the chemico-physical properties of the same. This is 
possible, for example, in the taking-uj) of fragments of contractile mus- 
cle substance, fibrin, 
and of bacteria which 
are either dead or die 
within the cell. In 
other cases such a 
nutritive process may 
be excluded, as in the 
case of insoluble dust. 
In the case of bacteria 
it may also happen 
that these are de- 
stroyed, but on the 
other hand they may 
multiply, and the re- 
sulting bacterial col- 
ony causes the death 
of the cell. 

The cells filled with 
foreign bodies are at first found in that place where the phagocytosis oc- 
curs, but they may wander further and often pass into the lymph- channels 
(Fig. 218, c) and lymph-glands (Fig. 220), and further into the blood-ves- 
sels, whence they are deposited, particularly in the spleen, bone-marrow, 




Fig. 219. —Phagocytes from granulation tis- 
sue with included leucocytes and fragments 
of same (sublimate, Biondi's stain) . a. Round, 
Z), spindle fibroblast with leucocytes ; c, d, e, 
fibroblasts containing remains of leucocytes. 
X 500. 




Fig. 320.— Collection of pigment-granule spherules in a lymph- 
gland (alcohol, carmine), a, Lymph-node; trabecula of the 
lymph-gland ; c, lymph-sinus with pigment-granule spherules. X 80. 



358 



INFLAMMATION. 



and liver (see § 20 and § 21). Other cells may reach the body surfaces, 
and the tissues may in this way be cleared of imi^urities. 

If the foreign bodies which have penetrated into the bod}^ from with- 
out, or if the dying or necrotic portions of tissue are too large to be 
taken up by leucocytes or proliferating tissue-cells, there often develop, 
in the granulation tissue formed in their neighborhood, multinuclear 
giant=cells, which arrange themselves on the surface of the foreign body 
or of the superfluous tissue-mass (Fig. 221, d), in exactly the same man- 
ner as is the case with osteoclasts under physiological conditions. If the 
bodies are not too large they may be taken up by these multinuclear cells. 
Otherwise the cells remain clinging to the surface, and, if the substance 
is soluble, gradually bring about its dissolution (for example, catgut 
sutures, fragments of dead muscle-libres). Occasionally it happens that 
mononuclear cells take up small foreign bodies into their substance, and 
afterward through division of their nuclei become converted into multi- 




FiG. 321.— Dog's hair encapsulated in the subcutaneous tissue (alcohol, Bismarck hrown). a, Hair; h, 
fibrous tissue ; c, proliferating granulation tissue ; d, giant-cells. X 66. 

nuclear cells. This event is most frequently observed after the taking- 
up of bacteria (leprosy, tuberculosis) which continue to multiply within 
the cells. 

If a foreign body lying within the tissues cannot be absorbed, it be- 
comes surrounded by granulation tissue, which later changes into con- 
nective tissue (Fig. 221, 6, c), and in this manner becomes encapsulated. 
In the case of smooth, insoluble bodies (glass beads) the proliferation 
may be very slight. 

The phenomena of chemotropismus or chemotaxis — that is, the attraction or 
repulsion of freely motile cells by chemical substances soluble in water — were first ob- 
served by Strahl and Pfeffer, who made researches particularly on mj^xomycetes, infu- 
soria, bacteria, spermatozoa, and zoospores. Investigations by Lehert, Massart, Bordet, 
Borissoio, Gabritschewsky, and others have shown that the leucocytes may also be at- 
tracted by chemical substances {positive clieinotrojnsmiis or chemotaxis) or repelled {nega- 
tive chemotropismus). There are in particular products of the vital activity of the 
fission-fungi {Lehert, Massart, Bordet, Gabritscliewsky), or bacterial proteids- — i.e., albu- 
minoid bodies of dead bacterial cells {Buchner)—yv\nc\i even after great dilution 
(according to Biichner, the protein of pyocyaneus is active when diluted 1:300) show a 
positive chemotaxis. According to Buchner, this property belongs also to gluten casein 
from wheat-paste, legumiu, bone-glue, alkali-albuminate from peas, while ammonium 
butyrate, trimethylamin, ammonia, leucin, tj^rosin, urea, and skatol exhibit negative 
chemotaxis. 

Literature, 

{Phagocytosis, Besorption, and Encapsidation of Foreign Bodies. ) 

Arnold: Staubinhalation u. fttaubmetastase, Leipzig, 1885; Ueber die Geschicke der 
Leukocyten in der Fremdkorperembolie. Virch. Arch., 133 Bd., 1893. 

Barfurth: Die Riickbildung des Froschlarvenscliwanzes. Arch. f. mikr. Anat., xxix., 
1887. 



PHAGOCYTOSIS, RESORPTION, AND ENCAPSULATION. 



359 



Earth: Knochenimplantation. Beitr, v. Ziegler, xvii., 1895. 
Bordet: Phagocytose. Ann. de I'lnst. Pasteur, x., 1896. 
Cassaet: De I'absorption des corps solides. Arch, de med. exp., iv., 1892. 
Fleiner: Resorption corpuscnlarer Elemente durch Lunge u. Pleura. Virch. Arch., 
112 Bd., 1888. 

Hamilton: On Sponge Grafting. Edinburgh Med. Jour., xxvii., 1882. 
Haug": Ueber die Organisationsfahigkeit der Schalenhaut des Hiihnereies, Miinchen, 
1889. 

Hallwachs: Ueber Einheilen von organischem Material. Langenbeck's Arch., 24 Bd., 
1879. 

Heidenhain: Histologic u. Physiologic d. Dilnndarmschleimhaut. Pfliiger's Arch., 
43 Bd., 1888. 

Hektoen: Absorption and Incrustation of Elastic Fibres in Giant Cells. Jour, of 
Med. Res., 1902; The Fate of the Giant Cells which Form in the Absorption of 
Coagulated Blood Serum, etc. Jour, of Exp. Med., 1898; The Fate of the Giant 
Cells in Healing Tuberculous Tissue. lb., 1898. 

Hildebrand: Secundare Implantation v. Haaren in Dermoidcysten. Beitr. v. Ziegler, 
vii., 1890. 

Hoffmann u. Langerhans: Verbleib in d. Circulat. eingefiilirten Zinnobers. Virch. 
Arch., 48 Bd., 1869. 

V. Ins: Exper, Unters. ilber Kieselstaubinhalationen. Inaug.-Diss., Berne, 1876. 
Kolliker : Die normale Resorption des Knochengewebes, Leipzig, 1887. 
Kriickmann: Fremdkorpertuberkulose. Virch. Arch., 138 Bd., Suppl. 1894. 
Langhans: Beobachtungen liber Resorption der Extravasate. Virch. Arch., 49 Bd., 
1870. 

Latis: Riassorbimento del catgut. La Riforma Med., 1891. 
Le Count: Cholesterin Giant Cells. Jour, of Med. Res., 1902. 

Lesser: Ueber das Verhalten des Catgut im Organismus. Virch. Arch., 95 Bd., 1884. 
Looss : Degenerationsercheinungen im Thierreiche, bes. uber die Reduction des Frosch- 

larvenschwanzes, Leipzig, 1889. Ref. Biol. Cbl, ix. 
Marchand, E.: Bildungsweise der Riesenzellen um Fremdkorper. Virch. Arch.; 93 

Bd., 1883. 

Marchand, F.: Einheilung von Fremdkorpern. Virch. Arch., 93 Bd., 1883. 
Metschnikoif : Unters. lib. die intracellulare Verdauung, Wien, 1883; Biol. Cbl., ii,, 

1883; Pathologic comparee de I'inflammation, Paris, 1892; La phagocytose mus- 

culaire. Ann. de I'lnst. Pasteur, vi., 1892; La resorption des cellules. lb., 1899. 
Meyer: Fremdkorperperitonitis mit Bildung von riesenzellenhaltigen Knotchen durch 

Einkapselung von Cholesterintafeln. Beitr. v. Ziegler, xiii., 1893. 
Museatello: Aufsaugungsvermogen des Peritoneums. Virch. Arch., 142 Bd., 1895. 
Nikiforoff: Bau und Entwickelung des Granulationsgewebes. Beitr. v. Ziegler, viii., 

1890. 

Noetzel: Histolyse. Virch. Arch., 151 Bd., 1898. 

Ochotin: Transplantation todter Knochentheile. Virch. Arch., 124 Bd., 1891. 
Ponfick: Studien iib. d. Schicksale korniger Farbstoffe im Organismus. lb., 118 Bd., 
1890. 

V. Recklinghausen: Ueber Eiter und Eiterkorperchen. lb., 28 Bd., 1863. 
Rindfleisch: Experimeutalstudien iiber die Histologic des Blutes, 1863. 
Roser, K. : Beitrage zur Biologic niederster Organismen, Marburg, 1891. 
Ruppert: Exper. Unters. lib. Kohlenstaubinhalation. Virch. Arch., 72 Bd., 1878. 
Salzer: Ueber Einheilung von Fremdkorpern, Wien, 1890. 

Slavjansky: Exper. Beitr. z. Pneumonokoniosislehre. Virch. Arch., 48 Bd., 1869. 
Sudakewitsch : Riesenzellen und elastische Fasern. Virch. Arch., 115 Bd., 1889; 

Modifications des fibres musculaires par la trichinose. Ann. de I'lnst. Pasteur, vi., 

1892. 

Virchow: Die Bildung der patholog. Pigmente. Virch. Arch., 1 Bd., 1847. 
Wasilieif-Kleimann: Resorption korn. Subst. durch. d. Darmfollikel. Arch. f. 

exp. Path., 27 Bd., 1890. 
Ziegler: Exper. Unters. iiber die Herkunft der Tuberkelelemente, Wiirzburg, 1875; 

Unters. uber pathologische Bindegewebs- u. Gefassneubildung, Wiirzburg, 1876; 

Ueber Proliferation, Metaplasie u. Resorption des Knochengewebes. Virch. Arch., 

73 Bd., 1878; Historisches u. Kritisches iiber die Lehre von der Entziindung. 

Beitr. v. Ziegler, xii., 1892; Ueber die Zweckmassigkeit der pathol. Lebensvorgange. 

Munch, med. Woch., 1896. 

See also §97; and for further literature concerning the behavior of body-cells 
toward bacteria, see Chapter X. ; and for further literature concerning the fate of trans- 
planted living tissue, see § 88, 



360 



INFLAMMATION. 



(Gheniotaxis, and Irritahility of the Leucoci/tes.) 



Bloch: Chemotaxis. Cbl. f. allg. Path., vii., 1896. 

Borissow: Chemotakt. Wirkung versch. ISubstanzen. Beitr. v. Ziegler, xv,, 1894. 
Buchner: Die cliemische Reizbarkeit der Leukocyteu uud dereu Beziehung zur Ent- 
ziiudung. Miinch. med. Woch., 1890, and Bed. klin. Wocli., 1890; Ref. Cbl. f. 
Bakt., ix., 1891; Pyogene Stoffe in d. Bakterienzelle. Berl. klin. Wocb., 1890; 
Die Entwickelung der Bakterienforschung seit Nageli's Eingreifen in dieselbe. 
Munch, med. Woch., 1891. 
Dineur: Sensibilite des leucocytes a relectricite. Soc. des sciences med. de Bruxelles, 



Gabritschewsky : Proprietes chimiotactiques des leucocj'tes. Ann. de I'lnst. Pasteur, 
iv., 1890. 

Lebert: Die Entstehung der Entzundung, Leipzis:, 1891, and Fortschr. d. Med., vii., 
1888. 

Massart et Bordet: Rech, sur I'irritabilite des leucoc3'tes, Bruxelles, 1890. 
Massart et Rodet : Le chimiotaxisme des leucocytes et I'infection. Ann. de I'lust. 
Pasteur, v., 1891. 

Pfeffer: Ueber chemotaktische Bewegungen Bakterien, Flagellaten u. Yolvocineen. 

Unters. a. d. botan. Institute zu Tubingen, ii., 1888. 
Woronin: Chemotaxis u, taktile Empfindlichkeit d. Leukocyten. Cbl. f. Bakt., xvi., 



§ 99. luflammation is, according to its nature, an acute process, but 
various conditions may cause the phenomena of tissue -degeneration and 

exudation to persist for a longer 



1892. 



1894. 



V. Chronic Inflammations. 




time, and the inflammation be- 
comes chronic. 



Fig. 233.— Necrosis of Qfteen years' duration in the 
lower part of the diaphysis of the femur, a, Seques- tO a 
trum ; b, c. edges of the opening in the thickened bone , 
(alcoholic preparation). Reduced one-third. 



The causes of chronic in= 
fiammations may be found, in 
the first place, in the fact that 
in the course of an acute inflam- 
mation there occur changes which 
prevent a rapid healing. In this 
sense, as may be deduced from 
the foregoing, act all large tis- 
sue defects and tissue necroses, 
as well as large masses of exu- 
date vrhich are with difficulty 
absorbable. When necrotic 
masses of tissue are not com- 
pletely absorbable, as in the case 
of large pieces of bone, they 
may indeed become sequestrat- 
ed, but persist as sequestra for 
years (Fig. 222, a), and keep up 
a constant inflammation. Fol- 
lowing the production of a large, 
superficial defect of the skin as 
a result of a burn, there devel- 
ops a granidation tissue, but 
months may pass before the 
wound surface is covered over 
with epithelium from the edges 
and the process thereby brought 




A further cause of chronic 



CHRONIC INFLAMMATION. 



361 



inflammation is found constantly in repeated injur 
For example, the frequently 
repeated inhalation of dust 
may cause chronic inflamma- 
tion of the lungs; repeated 
rubbing of the skin may 
cause a chronic inflammation 
of the part affected; patho- 
logical alterations of the 
stomach contents may cause 
chronic inflammation of the 
stomach. In the canals of 
the body in which concretio7is 
may form, the latter may 
give rise to lasting tissue- 
lesions. 

When there exist in a tis- 
sue unfavorable nutritive con- 
ditions — i.e., marked conges- 
tion — these may enable slight 
external influences, that under 
normal conditions either pro- 
duce no inflammation at all 
or one soon subsiding, to set 
up ulcerative jjrocesses show- 
ing no tendency to heal. In 
this manner, for example, 
chronic ulcers of the leg may 
arise. 

A very frequent cause of 
chronic inflammation is fur- 
nished by infections, particu- 
larly those caused by bacteria 
and moulds, which multiply in 
the body and thus constantly 
give rise to new inflammatory 
irritation. The inflammations 
which they cause are distin- 
guished from others chiefly 
by the fact that they usually 
show a progressive character, 
and form metastases through 
the lymph- and blood-vessels. 

Finally, chronic intoxica- 
tions form a last cause. These 
affect chiefly the kidneys and 
the liver, and may be attrib- 
uted either to the continued 
introduction into the organ- 
ism through the gastro- intes- 
tinal tract, lungs, or skin of 
substances harmful to the 
organs directly concerned or 
to others; or injurious sub- 



by external influences. 





Fig. 223.— L'hansres in the plpura and lung after a puru- 
lent pleuritis lasting six months (alcohol, orcein), a, 
Thickened lung tissue with gland-like alveoli, and elastic 
fibres in the newly formed connective tissue; h, thick- 
ened pleura; c, newly formed connective tissue without 
elastic fibres ; d, granulation tissue covered with pus ; e, 
elastic limiting membrane of the pleura: /, elastic fibres. 
X 46. 



362 



INFLAMMATION. 




Fig. 224.— Section of a stonecutter's lung with fibroid nod- 
ules (alcohol, picrocarmine). a. Group of fibroid nodules; 

normal lung tissue ; c, thickened lung tissue still containing 
bronchi, vessels, and a few alveoli. X 9. 



stances may be produced within the body itself, through disturbances of 
the processes of metabolism, thus giving rise to a chronic autointoxication. 

The forms of chronic inflammation are determined i)artly by their 
fundamental causes, partly by the character of the affected tissue. 

Chronic inflammations characterized especially by hyperplastic for= 
mations of connective tissue are found especially in the serous mem- 
branes, lungs, and external 
skin, but may occur also in 
other tissues. Chronic 
pleuritis, caused by exu- 
dates which are with diffi- 
culty absorbable, or by 
chronic infections, lead to 
extensive scar-like thickenings 
of the pleura (Fig. 223, h, c), 
the new-formation of tissue 
occurring in part upon the 
pleura (c) and in part with- 
in it (b). Moreover, indu- 
ration of the lung (a) may 
follow various infectious in- 
flammations, or may be 
caused by the continued in- 
halation of stone dust, in the 
latter case being character- 
ized by the formation of 
fibroid nodules (Fig. 224, a), in part also hj diffuse induration (c). 
Continued irritation in the neighborhood of the orifices of the urogenital 
apparatus, as through the discharge of irritating secretions, leads fre- 
quently to the formation of pointed condylomata {condylomata acuminata) 
— i.e., to a hyperplasia of the papillae and epithelium, in which the 
inflamed and infiltrated pa- 
pillse grow out with their 
vessels (Fig. 225, a, h) and 
frequently divide into 
branches. 

Frequently repeated or 
continued slight inflamma- 
tions of the skin and sub- 
cutaneous tissue, due to me- 
chanical lesions, parasites, or 
any other continued irrita- 
tion, may also, if they reach 
a considerable extent, give 
rise to a diffuse hyperplasia 
of connective tissue, which is 
known as elephantiasis. 

Inflammatory prolifera- 
tions of the periosteum and 

bone -marrow, which give rise to pathological neiv -formations of bone or 
a hyperostosis (Fig. 226), may be caused both by non-specific irritations — 
for example, by inflammations which run their course in the neighbor- 
hood of chronic ulcers — as well as by specific infections — for example, 
syphilis or tuberculosis. 




Fig. 225.— Condyloma acuminatum (injected preparation), 
o. Enlarged branching papilliB ; h, epidermis. X 20. 



VARIETIES OF CHRONIC INFLAMMATION. 



863 



Chronic catarrhs of the mucous membranes are sometimes caused by 
specific iufection (gonorrhoea, tuberculosis), sometimes by non-specific 
injuries (concretions, pathological changes in the gastric or intestinal 
contents), and sometimes by continued disturbances of circulation (con- 
gestion). 

Chronic abscesses arise usually from acute abscesses, and have the 
same etiology as the latter; but may also develop more gradually and are 
then caused by special infections, most fre- 
quently tuberculosis and actinomycosis. They 
are usually limited externally by a connec- 
tive-tissue membrane covered with granula- 
tion tissue, and may increase in size partly 
through the secretion of pus from the ab- 
scess-wall, and partly through the destruction 
of the wall and the neighboring tissue. Pro- 
gressive enlargement toward the deep -lying 
parts leads to the formation of burrowing or 
congestive abscesses. Their increase in size 
is always to be ascribed to the persistence of 
the infection. Perforation into neighboring 
tissues leads accordingly, also, to new infect- 
ive inflammations. 

The tuberculous and actinomycotic forms 
of chronic abscesses are distinguished from 
other forms partly by the specific characteris- 
tics of the pus and partly by the peculiar 
structure of the abscess-membrane (see Tuber- 
culosis and Actinomycosis, Chapter X.). 

Chronic ulcers are caused chiefly by spe- 
cific infections (tuberculosis, syphilis, gland- 
ers), but non-specific injurious agents may 
lead to chronic ulcerative processes in tissues 
which are especially susceptible to such 
changes. Thus chronic congestion in the 
vessels of the leg may have such an effect 
that ulcers arising through any mechanical 
influence may be prevented from healing un- 
der the unusual conditions in which the leg 
finds itself. Likewise peculiar qualities of 
the stomach contents may hinder the healing 
of an ulcer of the stomach. If healing be- 
gins at one edge of an ulcer while the ulcera- 
tion advances at other parts, there arises the 
form of ulcer known as serpiginous. The ex- 
cessive development of granulation tissue in 
an ulcer leads to the production of an ulcus 

elevatum hypertrophicum ; a dense callous, lardaceous thickening of tiie 
edge and base gives rise to the form known as ulcus callosum, or indolens, 
or atonicum. 

Chronic proliferations of granulation tissue — i.e., granulations which 
persist as such for a longer or shorter time without becoming changed into 
connective tissue — occur chiefly in various specific infections, the best 
known being tuberculosis, syphilis, leprosy, glanders, rhinoscleroma, and 
actinomycosis. Since the granulations in these infections often form 




Fig. 226.— Periosteal hyperostosis 
of the tibia, at the base of a chronic 
ulcer of the leg. Reduced two- 
flfths. 



364 



INFLAMMATION. 



fungoid proliferat-ions and tumor-like formations, they are often also 
called fungous granulations orcaro luxurians and infectious granula= 
tion tumors or granulomata. All these show certain peculiarities 
which enable us to recognize, from the structure, origin, and life-history 




Fig. 227.— Section through the mucosa of an atrophic large intestine (alcohol, alum-carmine), a. Glan- 
dular layer decreased to one-half its normal height; £», muscularis mucosae ; c, submucosa; d, muscularis; 
e, total atrophy of the mucosa. X 30. 

of the granulation-formation, also its specific etiology (see Chapter X.). 
It should be noted, however, that the etiology of some of the granulo- 
mata developing in the skin is still unknown. 

Chronic inflammations in which atrophy of the specific tissue is 




Fig. 228.— Induration and atrophy of the renal tissue in chronic nephritis (alcohol, alum-carmine), a. 
Thickened and fibrous capsule of Bowman ; /), normal glomerular vessels ; c, glomerulus whose vascular 
loops are in part impermeable and homogeneous, and the epithelium for the greater part lost ; d, com- 
-pletely obliterated glomerulus ; e, homogeneous masses of coagulation, arising from exudate and desqua- 
mated epithelium, and studded v^ith nuclei; /, desquamated glomerular epithelium; g, capsular epithe- 
lium; h, collapsed urinary tubule with atrophic epithelium; i, collapsed tubule without epithelium; 
hyperplastic connective-tissue stroma ; Z, cellular foci ; m, normal, somewhat dilated tubules ; n, afferent 
vessel ; o, vein, x 250. 



associated with hyperplasia of the connective tissue, occur particularly 
in the mucous membrane of the gastro -intestinal tract, and in the kid- 
neys and liver. 



RESULTS OF CHRONIC INFLAMMATION. 



365 



In the intestinal canal the cause may lie ia specific (dysentery) as 
well as in non-specific irritations ; the latter being dependent upon some 
abnormal property of the contents of the canal. The epithelial elements 
may undergo necrosis in association with persistent desquamation, the 
connective tissue being unaffected ; or they may necrose and disintegrate 
at the same time with the connective tissue upon which they rest. The 
final result is a mucous membrane (Fig. 227) which either contains no 
glands (e) or only rudimentary ones {a). 

In the liver and kidneys the chronic inflammations which lead to 
atroiDhy and induration, and whose final results are known as cirrhosis 
of the liver and indurated contracted kidney, are htematogenous dis- 
eases, in so far as they do not depend upon disturbances in the efferent 




Fig. 229.— Connective-tissue hyperplasia and proliferation of bile-ducts in chronic hepatitis (alcohol, 
hfematoxylin). a,ai, Liver-lobules; ft, hyperplastic periportal connective tissue; c, old bile-ducts: d, 
newly formed bile-ducts ; e, foci of small-celled infiltration. X .55. 

passages (obstruction, formation of concretions), and are caused partly 
by infections and partly by intoxications. They may begin either as acute 
inflammations or more insidiously ; and are characterized by atrophy and 
degeneration of the glandular tissue (Fig. 228, li, i), hyperplasia of the 
connective tissue (Fig. 228, a, Jc, and Fig. 229, b), through cellular infil- 
tration, formation of granulation tissue (Fig. 228, I, and Fig. 229, e), 
through obliteration of old vessels (Fig. 228, c, d), and through the for- 
mation of new vessels. In the liver there occurs also very frequently a 
formation of new bile-ducts (Fig. 229, d), which, however, for the greater 
part do not functionate. 



CHAPTER VIII. 



Tumors. 

I. General Considerations. 

§ 100. A neoplasm, or autonomous new=growth (Thoma), or tumor 
in the narrower sense, is a neiv-formation of tissue, apparently arising and 
growing independently, having an atypical structure, inserted uselessly into the 
organism, possessing no f unction of service to the body, and showing no typiccd 
termination to its growth. The atyi)ical character of the structure of a 
tumor is shown in its external appearance as well as in its internal or- 
ganization in that a true tumor departs more or less in structure from 
that of a normal organ. When this departure is but slight, the structure 
of the tumor approaches closely to that of the tissue-hypertrophies ; and 
there occur cases in which the diiference in structure is so little that it 
becomes very difficult to decide whether an excessive new-growth of tis- 
sue is to be classed as a tumor or an hypertrophy. 

Tumors may develop in any tissue of the body which is capable of 
growth, and arise through the proliferation of the tissue=cells, asso- 
ciated with a new=formation of blood=vessels. Xot infrequently there 
occurs also an emigration of leucocytes into the tumor, and exudative proc- 
esses and inflammatory tissue-proliferations may take place in its neigh- 
borhood, but these phenomena form no essential part of the development 
of the tumor. 

The processes of cell-division and new-formation of blood-vessels are 
the same as those described in §§ 81 and 83 — i.e., the division of the cells 
takes place by karyomitosis, and the new vessels are formed from buds 
given off by the proliferating cells of the walls of old vessels. The 
mitoses are for the greater part typical (Fig. 230, &), but there are also 
found relatively often atypical forms, such as asymmetrical divisions, 
nuclear figures with abnormally large chromatin masses (so-called giant 
mitoses), plurij)olar mitoses, and forms of nuclear fragmentation, and 
also direct segmentation. 

In their fully developed condition tumors are for the greater part well 
defined /ro?7i the surrounding tissues, but in some cases they may pass into the 
neighboring tissue ivithout any sharply defined border of transition. Further, 
an entire organ may become transformed into a tumor, or large poHions of 
tissue not sharply outlined from their surroundings may tal-e on the character 
of a tumor. Through the disintegration of tumor tissue there very fre- 
quently arise idcers. 

The difference between the structure of a tumor and that of normal 
tissue is usually recognizable even macroscopically, but there are also 
tumors which so closely resemble the parent tissue from which they arise 
that the difference can be made out only through a more careful exami- 
nation. 

The circumscribed tumors are usually nodular (Figs. 231, d ; 233, d, e ; 
231, a). The size of the single nodules varies, according to the kind of 

366 



GENERAL CONSIDERATIONS REGARDING TUMORS. 367 



tumor and the stage of development at the time of examination, from the 
smallest visible miliary and submiliary nodules to masses weighing ten to 
twenty kilograms or more. When situated upon the surface of an organ 
nodular tumors not infrequently take on the form of a sponge (Fig. 231, 
^) or of a polyp, and are accordingly designated /i^w^oi^Z or polypoid tu- 
mors. When a new-growth on the surface of a mucous membrane or the 
skin leads to an enlargement and branching of the papilla? there present, 
or if new papillse are formed, there arise warty ^ verrucose, and papillary 
tumors or papillomata (Fig. 232). A further development of the papillary 
structure may lead to a dendritic branching and the formation of a caidi- 
floiver mass. 

Tumors usually develop from small beginnings ; only rarely do they 
arise from centres extending diffusely throughout an entire organ. Their 




Tig. 330. — Tissue from a carcinoma of the breast, containing numerous division-figures in different phases 
of mitosis (Flemming's solution, safranin). a, Stroma ; b, epithelial plugs. X 500. 

growth may be either rapid or slow, and with occasional periods of qui- 
escence. Their growth may be suspended for years, and then suddenly 
again they become active. 

The structure of the tumor is determined by the parent tissue from 
which it takes its origiyi ; and although the true tumors always show a cer- 
tain atypical character, they yet retain certain characteristics of the parent 
tissue. 

According to their structure and genesis tumors may be divided into 
three groups: 1, connective-tissue tumors; 2, epithelial tumors; 3, teratoid 
tumors and cysts. It should be noted, however, that there are many forms 
of tumors which, according to the point of view, may be classed as be- 
longing to two, or even to all three groups. 

The connective=tissue tumors or the tumors arising from the sup= 
porting=tissue substances, and which are often called histoid tmnors, con- 
sist of tissues which in their structure correspond in part to mature and 
In part to embryonal connective tissue of the mesoderm, and moreover 
take their origin from mesodermal connective tissues. Ordinarily there 
21 



368 



TUMORS. 




are also included in this group those tumors arising from the specific 
elements of the nervous system — glia-cells and ganglion-cells— since these 
in their structure resemble the connective-tissue tumors much more than 

the}^ do the epithelial. 

The differences in 
the types of the con- 
nective - tissue tumors 
are essentially depen- 
dent upon the charac- 
ter of the ground-sub- 
stance, and in part also 
ui^on the cells. When 
the tumors are very 
rich in cells and the 
ground - substance but 
s 1 i g h 1 1 y developed, 
they acquire a soft con- 
sistency and are clas ^ed 
with t li e sa / -com at a . 
Very soft forms are 
designated as medullary 
or / u n g i mcdu Ua i 'cs. 
Through the combina- 
tion of different forms 
of connective tissue 
there arise mixed con- 
nective-tissue tumors. 

The epithelial tu= 
mors are composed of 
cells derived from sur- 
face epithelium or from gJand-ceUs, and also of vascidar connective tissue — 
which forms a supporting framework in the spaces of which the cells 
arising from the proliferation of surface epithelium or gland-cells lie in 
definite groups. Inasmuch as this arrangement gives to the tumors a 
structure suggesting that of a gland, they are often also called organoid 
tumors^ in contradistinction to the histoid connective-tissue tumoi s. It 
should be noted, however, that there are also included in the connec- 
tive-tissue group of tumors certain 
varieties (sarcomata) which have an 
organoid structure. 

The cells which give the epithe- 
lial tumors their especial character 
arise either from the ectoderm or en- 
toderm, and from the glands devel- 
oping from the same, or finally from 
the mesodermal epithelium of the 
pericardium, and of the pleural and 
peritoneal cavities, or of the glands 
arising from this layer (kidneys, 
sexual glands, adrenals). Tumors 
having the last-named origin often 

show more or less distinctly the especial character of the parent tissue 
from which they arise. 

Very soft cellular epithelial tumors are also designated medulkiry. 



Fig. 231.— Fungoid carcinoma of the endometrium of the posterior 
wall of the uterus, a. Body of the uterus ; b, cervix ; c, vagina ; c?, 
tumor. Two-thirds natural size. 




Fig. 232. 



Papillary adenoma of rectum. Nat- 
ural size. 



GENERAL CONSIDERATIONS. 



369 



Combinations of epithelial proliferations with i)roliferations of the 
connective tissne, Avhich exceed tlie ordinary amomit of supporting tis- 
sue or bear a sarcomatous character, lead to the formation of epithelial 
mixed tumors. 

' The teratoid tumors and cysts form a group which is especially 
characterized on the one hand by the fact that they contain the most 
varied kinds of tissue which may be derived from all three germ-laj ers 
{teratoid mixed tumors), and on the other hand by the presence of tissue 
formations in regions where they do not normally occur. Tumors, there- 
fore, which according to their structure maybe placed in one of the other 
groups, may be considered as teratomata on account of their situation. 
Further, there are also included in the group of teratoid tumors certain 
formations Avhich according to their structure, origin, and physiological 
relations ought not to be classed with the tumors. 

Tumors usually develop singly ; but it also happens that w ithin a 
certain tissue system there may appear either coincidently or in succes- 
sion a great number of tumors of the same kind, so that it must be 
assumed that the conditions requisite for the development of these tu- 
mors were present in different parts of the system affected. At times 
there develop in different organs of the same individual two entirely dif- 
ferent varieties of tumors, Avhich stand in no relation to each other, and 
whose coincident apx^earance is purely accidental. 

The exact deterniinatiou of wliat should be inchided under the term tumor is 
hardly possible ; and consequently the designation tumor is applied to many different 
formations which, according to their etiology, genesis, and life-characteristics, have not 
the same significance. The idea of tumor is, therefore, very differently conceived by 
different authors. I regard it as advisable, and also as based upon the life-characteris- 
tics of the tissue-formations which we are about to consider, to exclude in the first place 
from the class of tumors all hyperplastic proliferations, and further all retention-cysts 
which arise purely through the retention of secretions and show no independent new- 
formation of tissue. Further, according to my view, there should be separated from the 
true tumors all 'proliferatio)is of tissue due to the presence of parasites or to infection, par- 
ticularly the infectious granulomata which occur in tuberculosis, sj^philis, leprosy, etc. 
Should it be proved — which so far has not been done — that some of the new-growths 
now included with the true tumors are caused by infection, they should also be ex- 
cluded from the category of true tumors. 

The above classification of tumors is based essentially upon their histological 
character and histogenesis. They may of course be classified according to other points 
of view. Luharsch has offered the following classification with reference to the growth 
and behavior of the tumor: (1) Tumors which differ from the parent tissue in the 
arrangement of their elements, but for the chief part present no recognizable increase 
or at most only a transitory groAvth (various teratoid new-growths, misplaced tissue 
anlage, congenital mevi, many adenomata, myomata, fibromata, lipomata, chondro- 
mata, and osteomata); (2) tumors Avhich show a certain autonomy and independence in 
their structure, but yet on the whole obey the normal laws of life in that they alwaj's 
respect the ph vsiological tissue boundaries (myomata, adenomata, angiomata, lipomata) ; 
(3) tumors which are wholly emancipated from the physiological laws of life and rule 
in the tissues in total lawlessness of growth (carcinoma, sarcoma). 

The atypical structure of tumors is not given so much prominence by all au- 
thors as has been done above. This is particularly true with reference to those tumors 
which are similar in structure to the parent tissue from which they arise, and which are 
accordingly designated homoplastic tumors. If should be noted, however, that even in 
these tumors (chondroma, osteoma, fibroma, etc.) there occur in general, both in the 
histological structure, coarser organization, and external form, pronounced departures 
from the normal ; and, moreover, it may also happen that inflammatory proliferations 
caused by infection may show a structure similar to that of tumors. It is therefore 
not always easy to determine iwsitively whether a new-growth is to be regarded as a 
tumor. 

Tumors are in no sense useful to the organism as many tissue-hypertrophies 
may be. Tumor tissue does not possess the specific activity of that tissue from which 



370 



TUMORS. 



it springs, so that tumors can in no way be regarded as useful new-formations of tissue. 
It liappens, indeed, that in certain tumors there occur processes of secretion which 
correspond to normal secretions— thus, epithelial tumors may produce mucous or horny 
or colloid material (thyroid tumors), or bile-pigment (liver-tumors), even in metastatic 
nodules — but from these facts we can conclude only that, in many tumors which do not 
differ too greatly in structure from the parent tissue, the cells may retain, to a certain 
degree, for a number of generations, the functional capacities of the parent tissue. 
There is, however, no basis for believing that new useful tissue is formed as in the case 
of hypertrophy from increased labor; the products are for the chief part of no use to 
the body, and though perhaps in especial cases the colloid or bile so produced may be 
made use of, such a function must surely be of much less value than that of the normal 
tissue. 

The tumors arising from the mesodermal epithelium of the serous membranes or of 
the glands arising from these are included in the group of epithelial tumors. This is 
justified by the fact that such tumors correspond in their structure and clinical be- 
havior to the epithelial tumors of the ecto- and entoderm. I have also considered the 
question whether it would not be advisable (as Hansemann has proposed) to class also 
among the epithelial tumors — i.e., the adenomata and carcinomata — those tumors which 
have a framework of connective tissue, the spaces of which are filled, in a manner sug- 
gesting epithelial tissues, with cell nests arising from the proliferating endothelium of 
the blood- and lymph-vessels. Aside from the similarity in the structure of these tumors 
with the ordinary adenomata and carcinomata, there may be taken in favor of this view 
the fact that from the anatomical side the endothelium of the blood- and Ij'-mph-vessels 
is often designated as mesodermal epithelium. Against such a grouping of the endo- 
thelial with the epithelial tumors may be urged the facts that, aside from the general 
acceptance of the term endothelioma, the behavior of the endothelium of the blood- and 
lymph-vessels under pathological conditions is ver}^ different from that of epithelium, 
and that in many tumors it is impossible to separate the products of the growth of the 
endothelium of the blood- and lymph- vessels from the products of proliferation of con- 
nective-tissue cells. 

Literature. 

{Development of Tumors.) 

Adami: (Classification of Tumors.) Jour, of Path, and Bact., 1902. 
Alberts : Das Carcinom, Jena, 1887. 

Aoyoma: Indirecte Kerntheilung in verschiedenen Neubildungen. Yirch. Arch., 106 
Bd., 1886. 

Arnold: Kerntheilungen in den Zellen der Gescliwlilste. Yirch. Arch., 78 Bd. ; Kern- 

theilung und vielkernige Zellen. lb., 98 Bd., 1884. 
Bard: Anatomic pathol. generale des tumeurs. Arch, de phys., v., 1885. 
Brault: Gycogene dans les tumeurs. Arch, des Sc. Med., 1896; Le pronostic des 

tumeurs. L'CEuvre med.-ckir., 1899; Des tumeurs. Man. d'hist. path, de Cornil 

et Ranvier, i., 1901. 
Bucher: Multiple Carcinome. Beitr. v. Ziegler, xiv., 1893. 
Casper: Geschwlilste bei Thieren. Ergebn. d. allg. Path., iii., 1898. 
Cornil: Division indirecte des noyaux et des cell, dans les tumeurs. Arch, de phys., 

1886. 

Hansemann: Asymmetrische Zelltheilung in Epithelkrebsen. Virch. Arch., 119 Bd., 
1890; Pathologische Mitosen. lb., 128 Bd., 1891; Die Anaplasie der G^esclnvulst* 
zellen u. die asymmetrischen Mitosen. lb., 129 Bd., 1892; Die mikrosk. Diagnose 
der Geschwiilste, Berlin, 1897. 

Hauser: Das Cylinderepithelcarcinom, Jena, 1890. 

van Heukelom: Sarkome u. plastische Entziindung. Yirch. Arch., 107 Bd., 1887. 
Kaufmann: Multiplicitat d. prim. Carcinoms. Yirch. Arch., 75 Bd., 1878. 
Kelynack : Renal Growths, Edinburgh, 1898. 
Klebs: Allgem. pathol. Morphologic, Jena, 1889. 
Lancereaux: Traite d'anat. pathol., i., Paris, 1877. 

Lang-lians: Ueber Glykogen in pathologischen Neubildungen. Yirch. Arch., 120 
Bd., 1890. 

Lannois et Courmont: Deux cancers primit. du tube digestif. Rev. de med., 1894. 
Lubarsch: Hyperplasie u. Geschwlilste. Ergebn. d. allg. path. Morph., Wiesbaden, 

1895; Zur Lehre v. d. Geschwlilsten, Wiesbaden, 1899. 
Luecke u. Zahn: Chirurgie d. Geschwlilste, i., Stuttgart, 1896. 

Marchand: Bezieh. d. path. Anat. z. Entwickelungsgesch. Yerh. d. Deut. path. 
Ges., ii., Berlin, 1900. 



ETIOLOGY OF TUMORS. 



371 



Martin: Zur Keiintniss der indirecten Kerntlieiking. Vircli. Arch., 86 Bd., 1881. 
Mtiller: Celliilare Vorgange in Geschwiilsten. Vircli. Arch., 130 Bd., 1892. 
Miiller, J. : Ueber den feiueren Ban und die Formen der kraukh. Geschwiilste, 1883. 
Paget: Lectures on Tumors, 1852. 

Petrone: Breve guida alio studio dei tumori, Catania, 1890. 
Pfitzner: Zur patliolog. Anatomie des Zellkerns. Virch. Arch., 103 Bd., 1886. 
Schimmelbusch : Multiples Auftreten prim. Carcinome. Langenbeck's Arch., 39 
Bd., 1889. 

Scliniidt: Secretionsvorgitnge in Krebsen. Virch. Arch., 148 Bd., 1897 (Lit.). 
Senn : Pathology and Surgical Treatment of Tumors, 1895. 

Strobe: Kerntheilung und Riesenzeilenbildung in Geschwiilsten. Beitr. v. Ziegler, 
vii., 1890; Cellulare Vorgange u. Erscheinungen in Geschwiilsten. lb., xi., 1891; 
Neuere Arbeiten iiber Histogenese u. Aetlologie des Carcinoms. Cbl. f. allg. 
Path., ii., 1891. 

Thiersch.: Der Epithelkrebs der ausseren Haut, 1865. 

Thoma: Allgem. patholog. Anatomie, Stuttgart, 1894. 

Trambusti: Bau u. Theilung der Sarkomzellen. Beitr. v. Ziegler, xxii., 1897. 
Virchow: Die krankhaften Geschwiilste, i.-iii., 1863-67. 
Wells: Multiple Primary Tumors. Jour. Path, and Bact., 1900 (Lit.). 
White: The Definition, Terminology, and Classification of Tumors. Jour, of Path., 
vi., 1899. 

Williams: The Principles of Cancer and Tumor Formation, London, 1889. 
Wilms: Die Mischgeschwiilste, i., ii., Leipzig, 1899, 1900. 
See also 101 and 102. 

§ 101. The etiology of tumors is by no means uniform, and very 
often cannot be determined AYith certainty. In the majority of cases, 
however, the conditions, at least, under which the new-grow^th appeared 
can be assigned and w^e may accordingly establish different groups of 
tumors. Infectmi is indeed very frequently advanced as a cause of tu- 
mors, but such etiology has not in any case been demonstrated beyond 
doubt. 

As the first group of tumors, according to etiology, may be taken those 
arising from especial congenital milage, so that we may in a certain sense 
regard them as local malformations of tissue. They develop either in 
uterine life, and are present at birth, or later in extra-uterine life, dur- 
ing the period of growth or even later, in which case trauma not infre- 
quently gives the immediate occasion for the beginning of the develop- 
ment of the tumor from the preexisting anlage. 

To this groui3 belong in the first place many osteomata, chondromata, 
angiomata, gliomata, fibromata (of the nerves and skin), sarcomata and 
adenomata. Further, many teratoid tumors and cysts are also to be 
included in this group, inasmuch as they represent in part either re- 
mains of foetal structures, transpositions or monogerminal inclusions of 
embryonic tissue, implantations of rudimentary portions of a twin em- 
bryo (bigei-minal implantations), or probably also the results of disturb- 
ances of the earliest stages of the development of the ovum. 

A second group develops after traumatic injuries of the tissues ; aud.it has 
been reckoned that in about seven to fourteen per cent of cases a trau- 
matic origin can be assigned ; particularly in the case of sarcoma, carci- 
noma, and osteoma. The causes of the tumor-formation may be a single 
injury, a stab, a blow, crushing, fracture, etc., as well as reiDcated me- 
chanical irritation, such as rubbing, scratching, etc. 

I7i a third group the development of the tumor follows inflammation, par- 
ticularly the formation of gramdation tissue with suhsequent cicatrization. The 
inflammation and ulceration may be caused by non-specific as well as by 
specific injurious agents. For example, cancer of the gall-bladder (Fig. 
233, d, e) almost invariably develops only in gall-bladders which contain 



372 



TUMORS. 



stones, and are consequently the seat of chronic inflammation. In the 
stomach, cancer may develoi) in tlie ediie of an nicer or in the scar of one 
after healing has occurred. In the external skin and also in the mucous 




Fig. 233,— Primary carcinoma of the gall-bladder enclosing an impacted gall-stone. Frontal section 
tlirougli the gall-bladder and liver, a. Liver ; b, duodenum ; c, gall-stone ; (7, wall of the carcinomatous 
gall-bladder ; e, cancerous infiltration of the neighboring liver tissue ; f. portion of duodenum which is in- 
filtrated with cancer and adherent to the gall-bladder tumor. Natural size. 

membranes of the pharynx and larynx cancers occasionally arise in the 
base of a tuberculous or syphilitic granuloma or in the scar of such a 
process. 

In a fourtli group the development of the tumors appears to owe its origin 
to an unequal atrophy of the elements whieh mal'e uj) a tissue, so that eertain 
hindranees to growth are removed or lessened. Here belong especially cer- 
tain epithelial proliferations {eaneers) which develop in old age, or in organs 
which after a period of increased activity become atrophic. In this way, 
for example, the development of cancer of the skin may be explained on 
the ground that the connective tissue of the skin undergoes a certain 
retrogression leading to a relaxation of its structure, while the epitlif^lium 
is still possessed of its full power of proliferation. 

It cannot be doubted that the etiology of tumors is not always tlie same, as is 
shown by the variety of conditions under which they arise. 

It is difficult to say what is the nature of the influence which excites the cells to 
the production of un aiifpiad tissue. We are at first inclined to think of the same causes 
Avhich underlie hypertropln' and regeneration of tissue, also, on the one hand, of espe- 
cial congenital anlage or of stimuli which increase the formative activity of the cells, 



ETIOLOGY AND GENESIS OF TUMORS. 



373 



and on the other hand, of a lessening or removal of hindrances to growth. But it still 
remains a problem why there should not be formed typical tissues which would so fit 
into the organization of the body that they would be of service to the latter. In the 
attempt to explain this phenomenon, which is at the same time associated with an in- 
crease in the vital and reproductive capacities of the cells, even under pathological con- 
ditions (metastasis of the cells through the blood- and lymph-vessels), many writers 
have sought and would recognize as the cause the presence of parasites (see Etiology 
of Carcinoma) ; but our present knowledge does not in any way justif}^ us in attributing 
the development of true tumors, of autonomous new-growths, to the influence of para- 
sites. On the contrarj^ the development and life-history of tumors, and in particular 
the formation of metastases, which without doubt arise through the multiplication of 
living tumor-cells transported in the lymph- or blood-stream, speak against the hypoth- 
esis of the parasitic nature of tumors. 

CohnTu'iiu advanced the theory that all true tumors arose from especial tumor- 
anlage which had their origin in the persistence of foci of embryonal tissue. Neither 
the results of clinical observation nor of the anatomical investigation of the tissues 
speak in favor of such a theory. 

Ribbert is of the opinion that the cause of the pathological proliferation which leads 
to tumor-formation is to be found particularly in a separation of cells or cell-groups 
from their organic relations, such a separation occurring either as the result of intra- 
uterine disturbances of development or later under the influence of external agencies. 
Nevertheless, such transplantations or separations of cell-groups take place very fre- 
quently in intra-uterine life, or after trauma, after ulceration, in scars and in infectious 
granulomata, without any subsequent development of a tumor. These transplanta- 
tions of tissue constitute only one of the predisposing causes of tumorformation, but some 
other factor is necessary to excite the atjqDical progressive tissue-proliferation — i.e., the 
development of the tumor. The development of a tumor is, therefore, in no icise depen- 
dent upon, a transplantation of tissue ; rather does the tumor-proliferation take its origin in 
cells irliich are normally situated ; and this may be actually demonstrated, particularly 
in the case of epithelial tumors. 

Our knowledge of the causes of tumor-development at the present time may be summed 
up as follows : Inherited and acquired conditions of certain cells and cell-groups, which 
assert themselves in a tendency to increased formative activity with the production of 
atypical tissue, lead to the formation of tumors. In many cases this proliferation is 
prepared for, favored, and excited by the transplantation of cells and cell-groups, but 
often also through changes in the neighborhood of the cells concerned. No general 
scheme applicable to the development of all tumors can be given. On the contrary, 
the conditions vary not only with the different forms of tumors, but also with the indi- 
vidual cases of the same tumor-type. Moreover, it should not be forgotten that the 
formations which we class as tumors do not all possess the same significance, and that 
many of the same ought more properly to be classed with other phenomena of growth 
(malformations). 



Literature. 

(^Etiology and Genesis of Tumors. ) 

Adami: On Growth and Overgrowth, etc. Med, Chron., 1900; Concerning the Causa- 
tion of Cancerous and Other New-Growths. Yale Med. Jour., 1901. 

Askanazy: Geschwlilste d. in d. Niere eingeschloss. Nebennierenkeime. Beitr. v. 
Ziegier, xiv., 1893. 

Beneke: Neuere Arbeiten z. Lelire vom Carcinom. Schmidt's Jahrb., 234 Bd., 1892. 
Bog-ehold: Entwickelung von malignen Tumoren aus Narben. Vircli. Arch., 88 Bd,, 
1882. 

Boll: Das Princip das Wachsthums, Berlin, 1876. 

Bonnet: Zur Aetiologie der Embryome. Mon. f. Gebh., 1901. 

Borsch: Pathogenese d. malignen Geschwlilste. Virch. Arch., 162 Bd., 1900, 

Buxton: Enzymes in Tumors. Jour, of Med. Res., 1903. 

Coh.nh.eini: Yorlesungen fiber allgemeine Pathologic, Berlin, 1882. 

Crone: Lupuscarcinora des Kehlkopfs. Arb. a. d, path. Inst. v. Baumgarten, ii., 1894. 

Czerny: Warum diirfen wir die parasit. Theorie filr die bosart. Geschwulste nicht 

aufgeben? Beitr. v. Bruns, xxv., 1899. 
Foa: Sui parassiti et sulla istologia patologica del cancro. Arch, per le Sc. Med., 

xvii., 1893. 

Gerhardt: Das Gliom. Festschr. zur dritten Sacularfeier d. Universitat, Wiirzburg, 
ii., 1882. 



374 



TUMORS. 



Haberern: Daten zur Lehre von den Callustumoren. Langenbeck's Arch., 43 Bd., 
1893. 

Hansemann: Specificitat, Altriiismus u. Anaplasie der Zellen, Berlin, 1893. 
Hauser: Das chron. Magengeschwiir., Leipzig, 1883 ; Das Cylinderepithelcarcinom des 

]Magens u. d. Darms, Jena, 1890; Histogeuese d. Platteuepitbelkrebses. Beitr. v. 

Ziegler, xxii., 1897. 
Heg-ar: Zur Aetiologie bosart. Gescbwulste. Beitr. z. Gebh., iii., 1900. 
Kabane: Tlieorie des Careiuoms. Cbl. f. allg. Patb., vi., 1895. 
V. Karwowski: Ueber Calbistumoren. Inaug.-Diss., Freiburg, 1895. 
Kenibacbieif: Carcinom nacb Lupus. Inaug.-Diss., Freiburg, 1893, 
Kirmisson: Cliirurgiscbe Ki'ankbeiten angeborenen Ursprungs, IStuttgart, 1899. 
Kocber: Krankh. d. mannl. Gescblecbtsorgane. Dtscb. Chirurgie, Lief. 50b, 1887. 
Kiister: Fragen d. patb. Ptianzenanatomie (Gallenbiklung). Biol. Cbl., xx., 1900. 
Liebe: Tlieer- und Parafflnkrebs. Schmidt's Jahrb., 236 Bd., 1893. 
Levin : Cell Proliferation under Pathological Conditions with Especial Reference to the 

Etiolog}' of Tumors. Studies from Dept. of Path., Columbia University, 1901-02. 
Lowentbal: Traumatische Entstehung v. Geschwulsten. Arch. f. klin. Cliir., 49 Bd., 

1895. 

Petersen u. Exner: Hefepilze u. Geschwulstbildung. Beitr. v. Bruns, xxv., 1899. 
Pianese: Beitr. z. Histologic u. Aetiologie d. Carcinoms. Beitr. v. Ziegler, Suppl., 
1896. 

V. Recklingbausen : Adenomyome u. C3^stadenome d. Uterus, Berlin, 1896. 
Ribbert: Histogeuese d. Carcinoms. Virch. Arch., 135 Bd., 1894; Die Entstehung d. 

Geschwlilste. Deut. med. Woch., 1895; Das patholog. Wachsthum d. Gewebe, 

Berlin, 1896; Ueber Rlickbildung v. Zellen u. Geweben u. die Entstehung v. 

Geschwulsten, Stuttgart, 1897. 
Scbubert: Ueber den primaren Gallenblasenkrebs. Inaug.-Diss., Freiburg, 1893. 
Scbubardt: Entstehung der Carcinome aus chron. -entziindlichen Zustanden, Leipzig, 

1885, 

Scbulthess: Statistische L^ntersuch. iib. d. Aetiologie d. Carcinoms. Beitr. v. Bruns, 
iv., 1881. 

Sieg-ert: Aetiologie des Gallenblasenkrebses. Yirch. Arch., 132 Bd., 1893. 

Stern: Maligne Tumoren im Kindesalter. Deut. med. Woch., 1892. 

Strobe: Neuere Arbeiten liber Histogeuese u. Aetiologie des Carcinoms. Cbl. f. allg. 
Path., ii., 1891; Die parasitaren Protozoen in ihren Beziehungen zur menschl. 
Pathologic, insbes. zur Histogeuese u. Aetiologie des Carcinoms (Ref.). lb., v., 
1894; Entstehung d. Gliome. Beitr. v. Ziegler, xviii., 1895. 

Tauffer: Sarkome auf narbig luposem Boden. Yirch. Arch., Suppl., 151 Bd., 1898. 

Volkmann: Krebs d. Extremitaten. Samml. klin. Vortr., Nos. 334, 335, 1890. 

Weisflog-: Ueber Callustumoren, Beitr. v. Bruns, x., 1893. 

Wilms: Die teratoiden Geschwlilste d. Hodens. Beitr. v. Ziegler, xix,, 1896. 

V. Winiwarter: Beitr. z. Statistik d. Carcinome, Stuttgart, 1878. 

Wieland: Primare multiple Knochensarkome. Inaug.-Diss., Basel, 1893. 

Wolff: Zur Entstehung d. Geschwlilste nach traumatischen Einwirkungen. Inaug.- 
Diss., Berlin, 1874. 

Wiirz: Traumat. Entstehung der Geschwlilste. Beitr. v. Bruns, 26 Bd., 1900 (Lit.). 
Zabn: Zur Aetiologie der Epithelkrebsc. Virch. Arch., 117 Bd., 1889. 
Zenker: Der Krebs d. Gallenblase. Deut. Arch. f. kbn. Med., 44 Bd., 1889. 
Ziegler, P.: Bezieh. v. Traumen zu malignen Geschwulsten. Miinch. med. AYoch., 
1895. 

See also §100. 

§ 102. Wbeu once a tumor has arisen in any tissue and has reached a 
certain stage of development it may become quiescent in growth, and 
remain for a life-time without undergoing further change. This is true 
particularly of those tumors which according to their origin are re- 
garded as local tissue -malformations : but tumors which develop first in 
later life may also come to a standstill after attaining a certain size. 

The growth of a tumor takes place independently, and in many 
cases continues even until death occurs. 

From the surrounding tissues the tumor acquires both its blood-ves- 
sels and thereby its food material, but may besides grow independently 
— i.e., through an increase of the cells which form the elements of the 
tumor. In many cases the tumor increases in size essentially through an 



INFILTRATION AND METASTASIS. 



375 



interstitial expansive growth, and the neighboring tissue is only 
crowded or pushed aside. In other cases the tumor tissue grows by 

infiltration and /orces its ivay into the intercellular spaces of the neighboring 
tissue, so that new areas of tissue are thus brought under the influence of 
the tumor. In this way the cells of the newly invaded tissue are often 
excited to proliferation, so that an enlargement of the tumor takes place 
through an oppositional groivth, in which both the cells of the original 
tumor and of the surrounding tissue take part. 

The characteristic feature of growth by infiltration consists in the 
involvement of the tissues of the organ which lie in the neighborhood of the 
primary tumor. Further, the tissue of neighboring organs (Fig. 233, e, f) 




Fig. 334.— Section through a primary cancer of the liver (a), with multiple metastases (b) within the liver 

itself. Three-sevenths natural size. 

may become involved by the tumor through its spread by contiguity. If 
tumor-cells gain entrance into the great body-cavities they may spread over the 
serous surfaces and lead to the development of tumors. 

If, in the process of infiltration, a tumor gains entrance into a lymph- or 
blood-vessel — an event which in particular is always likely to occur in the 
case of the tumors called carcinoma and sarcoma — and if living tumor- 
cells capable of proliferation are transported through the lymph- or blood- 
vessels, there often arise turnor=metastases — i.e., a development of 
daughter=tumors which are not directly connected with the primary 
tumor. The daughter-tumors may at first develop in the organ primarily 
affected (Fig. 234, but usually soon involve other organs as well ; in 
the case of rupture into the lymph-vessels the lymph-glayids are first 
affected ; in rupture into the blood-vessels, those organs to which the blood 
carries the living cells. The direction of the transportation is usually that 
of the lymph- and blood-stream, but retrograde transportation not infre- 
quently occurs, particularly in the lymph-vessels, the lumina of which 
are easily obstructed by tumors. 

The development of daughter=tumors takes place in all cases from 
transported cells. In the event of metastasis by the lymph=vessels 
the affected lymph- vessels (Fig. 235, a) are first filled with cells, which 



3Y6 



TUMORS. 



develop from the transported tiinior-cells. Later there follow a pro- 
liferation and new-formation of blood-vessels on the part of the neigh- 
boring tissue, and as a result of these processes there develop larger or 




Fig. 235.— Periglandular lymph-vessel (In the axillary region) filled with canoer-oells arising from a 
primary carcinoma of the mammary gland (Miiller's fluid, ha?matoxvliu). a, C ancer-relb ; /^ 'wall of 
lymph-Vessel. X 300. 

smaller nodules. It also not infrequently happens that the lymph -vessels 
are more uniformly distended hy the growth (Fig. 235, a), without any real 
formation of nodules, or at least only small swellings dev elop along the 
course of the lymi^h- vessels. In the event of metastasis into lymph-glands 




Fig. 236.— Metastatic development of cancer in the branches of the portal vein and liver-capillaries 
Oliiller's fluid, haematoxylin, and eosin). a, Liver tissue ; ?j, plugs of cancer-cells in the portal vein ; c, 
cancer-cells in the capillaries. X 100. 

the latter become swollen, forming nodules of smaller or larger size, in 
which the tissue of the lymi^h-giand is gradually rej^laced by tumor 
tissue. 

In the case of metastasis through the blood=vessels the first develop- 
ment of the secondary tumor begins with the tumor-cells forming the em- 



METASTASIS OF TUMORS. 3T7 

bolus iu artery, capillary, or vein, and under certain conditions the ves- 
sels (Figs. 236, h, c ; 237, h, c) may be filled and greatly dilated by the 
13roliferating tumor-cells. The tissue in which the tumor-embolus 
develops may at first remain passive, and the specific tissue-elements — 
gland-cells (Fig. 237, d) and muscle-cells — may vanish as the result of 
increasing atrophy. Later, the blood-vessels and connective tissue take 
part in the development of the secondary tumor. 

In the further course of its development the secondaiy nodule is 
usually sharply circumscribed from its surroundings and grows by ex- 
pansion. It, however, not infrequently hapi^ens that, at least in places, 




Fi(i. 2or.— Mt'tastati<' sarcdiiia (if tlit" livci' fnnii a priniarv sai-coina nf ilie parotid ( Flfinniiiig's solution, 
safi'anin, picric acid), f/, I jvci-i-ods ; sarcuma lissiic dc\ dnpintr wji hin liic vessels ; r, isolated tiiinor- 
cells ill the liver-caitillai-ics ; (/, livcr-ccUs which lia\c uudci>;<)iic arroijhy and i'atty degeneration. X 150. 

the infiltrative growth persists, and under certain conditions widespread 
diffuse tumors develop, particularly in the bone-marrow and in the liver 
(Fig. 237). 

The number of lymj)hogenous and hiematogenous metastases varies 
greatly in different cases. At one time the metastases may be confined 
to one organ, at other times they may be scattered throughout several. 
In rare cases cells of the original tumor may be spread through almost 
the entire body, so that in the most diverse organs — glands, muscles, 
skin, etc.— larger and smaller nodules may appear in quick succession. 
This phenomenon is possible when tumor-nodules situated in the lung, 
pleura, or bronchial glands break into a pulmonary vein. 

If a living bit of tumor capable of forming metastases is transplanted 
from one animal into the tissues of another animal of the same species, it 
sometimes happens that it will develop in the second animal. There 
may take place, therefore, a metastasis from one animal to another. In 
man, tumor particles may in a similar manner be transplanted during 
operations from one part of the body to another and there continue to 
grow. 

Side by side with the progressive i3roliferation of tissue there very 
frequently occur in tumors retrogressive changes, particularly in 
rapidly growing and infiltrating cellular tumors, in which fatty and 
mucous degeneration, necrobiotic j)rocesses, and haemorrhages may take 



378 



TUMORS. 



pUice to a marked degree, so ttiat there not infrequently results a total 
destruction of the tumor tissues. This rapid disintegration of the tumor is 
in part due to the fact that in carcinomata the epithelial proliferation to 
a very great extent grows into the blood-vessels and so obstructs them. 
In the case of nodular tumors the destruction of the tumor-cells, when 
followed by a resorption of the products of degeneration, leads to shrink- 
ing and to the formation of cicatricial contractions. Very often degener- 
ation-cysts and ulcers may be thus formed ; and particularly in the case 
of carcinomatous tumors of the mucous membranes the parts of the 
tumor growing up above the surface very often for the greater part un- 
dergo disintegration. In slowly growing tumors of hard consistency 
extensive retrograde changes do not usually occur. 

The necrosis and disintegration of the tissues of the tumor only very 
rarely terminate in a cure. This event is most likely to happen when a 
polypoid new-growth becomes totally necrotic (for example, as a result 
of twisting or tearing of its pedicle) and is thrown off. In the majority 
of the tumors showing a tendency to retrogressive changes and disinte- 
gration, while the older portions are dying the growth constantly ad- 
vances at the periphery, so that new 
tissues are being progressively at- 
tacked by the tumor. 

If the tumor is extirpated, there 
may result a cure when all of the 
growth has been removed or de- 
stroyed. This is most easily accom- 
plished in the case of slowly growing 
and shai-ply circumscribed tumors 
which increase by expansion. In the 
case of infiltrating tumors it is very 
difficult to detei-mine the boundary 
of the tumor-growth, since this may 
often extend far beyond the point 
where any macroscopic change in the 
tissue is apparent. Consequently, in 
such cases there takes place, sooner 
or later, in the operation scar a re= 
currence (Fig. 238, a) which arises 
from portions of the tumor remaining 
in the tissues. Such recurrences be- 
have exactly like the primary tumor, 
and may also form metastases (Fig. 
238, c).^ 

According to their clinical and 
anatomical characteristics tumors 
may be classed as benign and malig= 
nant. As benign tumors are generally 
Ficx 238.-Re('unt"nt siiivoina in tiie aniputa- re^'ardcd thosc wh icJi qrow sJoidii and hii 

tion-stump of tbe femur, a, Fmigoui tumor * . ^ f ^' 

arising from the bone-marrow; />, periosteal expa}tSI0n and dO UOt forni lliCtastaSCS ^ 
noclules ; c, metastasis, une-laalf natural size. malignant, tJwSC wMch shoW a Complete 

emancipation from the no)-mal laws of 
proliferation, grow quickly and by infiltration, easily undergo degenerative 
changes and form metastases. According to the investigations of Brault, 
the cells of rapidly growing tumors are rich in glycogen ; in those of slow 
growth, and after the inception of retrogressive changes, it is absent. 





MALIGNANCY. 



379 



The malignant tumors, on the whole, coincide with those tumor 
forms which are known as carcinoma and sarcoma. It must, however, 
be borne in mind that the malignancy of a tumor depends not only upon 
its character, but also uj)Ou its location. A benign tumor takes on a 
malignant character as soon as its presence interferes with the functions 
of vital organs. Hence every tumor of the brain or meninges becomes a 
dangerous affection at the moment when it gives rise to disturbances of 
the cerebral functions. Under certain conditions such benign tumors as 
fibromata of the uterus become destructiv e growths as soon as they reach 
such a size as to displace and compress the neighboring organs. 

After a tumor has existed for a certain period there results very 
frequently a marked lowering of the general nutrition, a marasmus, 
which is usually designated tumor=cachexia. This occurs chietly in 
association with the malignant growths known as cancer and sarcoma ; 
and may depend, in part at least, w^ow the great demands made upon the 
food supply by the rapid growth of the tumor, particularly in the case 
of formation of metastases. A still more important cause may lie in the 
fact that the tumor may interfere with the taking-in of food. In cancer 
of the oesophagus, stomach, and intestine the function of the affected 
organ is greatly interfered with, and the assimilation of food may be 
entirely iDrevented or nearly so. Further, it should be borne in mind 
that through the degeneration of the tumor and the continuous secretion 
from the resulting ulcers large amounts of albuminous material may 
often be lost from the body ; and that through putrid decomposition 
there may arise substances which, when absorbed, may act injuriously 
upon the organism. Finally, the pain which is often felt in a tumor 
may rob the patient of his sleep, \yhether the tumor itself, in certain 
cases, produces substances harmful to the organism is yet unknown, but 
is, however, not improbable. 

Literature. 

{Tumor -Metastasis. ) 

Acker: Zur Patliogeiiese d. Geschwulstmetastase. Deut. Arch. f. klin. Med., xi., 
1873. 

Andre: Entsteh. d. Geschwnlstmetastasen auf embolischem Wege. Virch. Arch., 61 
Bd., 1874. 

Arnold: Ueber rlicklaufigen Transport. Vircli. Arch., 124 Bd., 1891. 
Audibert: De la generalisat. dii cancer de I'estomac, Paris, 1877. 

Beneke : Freies Wachsthum metast. Geschwulstelemente in serosen Hohlen. Deut. 

Aicli. f. klin. Med., 64 Bd., 1899. 
Geissler: Uebertragbarkeit d. Carcinoms. Langenbeck's Arch., 46 Bd., 1893. 
Goldmann: Verbreitungawege bosartiger Geschwillste. Beitr. v. Bruns, xviii., 1897. 
Hanau: Erfolgreiche exp. Uebertrag. v. Carcinom. Fortschr. d. Med., vii., 1889. 
Just: Ueb. d. Verbreit. d. melanot. Geschw. im Lymphgefasssystem. Inaug.-Diss., 

Strassburg, 1888. 

Kantorowicz: Pathogenese der allgemeinen Carcinomatose. Cbl. f. allg. Path., Iv., 
1893. 

Lanz : Uebertragbarkeit melanot. Geschwiilste. Festschr. f . Kocher, Wiesbaden, 1891. 
Morau: Rech. exp. sur la trausmissibilite de certains neoplasmes. Arch, de med. 
exp., 1894. 

Perls: Beitr. z. Geschwulstlehre. Virch. Arch., 56 Bd., 1872. 

Petrick: Verbreitung d. Carcinoms in den Lvmphdriisen. Deut. Zeitschr. f. Chir., 
32 Bd., 1891. 

Rieder: Ueber die embol. Geschwulstmetastase. Inaug.-Diss., Dorpat, 1878. 
Velich.: Uebertrag. v. Rattensarkom auf andere Ratten. Wien. med. Bl., 1898. 
Virchow: Die krankh. Geschwiilste, i.-iii., 1863-67. 

Weber: Zur Geschichte des Enc-hondroms, namentl. in Bezug auf dessen hereditares 



380 



TUMORS. 



Vorkommen u. sccund. Verbreit. iu inueren Organen (lurch Embolie. Virch. 
Arcliiv, 35 Brl., 1866. 

Winkler: Bethcil. d. Lymphgefiissc an d. Metastase. Virch. Archiv, 151 Bd., Siippl., 
1898. 

Zahn: Ueber Geschwulstmetastasen. Virch. Archiv, 117 Bd., 1889. 
Zenker, K. : Zur Lelirc v. d. Metastasenbildung d. Sarkome. Virch. Arcliiv, 120 
Bd., 1890. 



II. The Different Forms of Tumors. 



I. Tumors Derived from Connective Tissue or the Supporting- 
Framework. 




Fig. 339.— Hard fibroma from lobe of the ear (alco- 
hol, hfematoxylin). a, Longitudinal section ; &, trans- 
verse section of bundles of tlbres. X 4< K». 



(a) Fibroma. 

§ 103. A fibroma is a tumor composed of fibrous connective tissue. It 
occurs most frequently in the form of nodules, which are sharply circum- 
scribed from the surrounding tis- 
sues, and usually involve but a 
portion of the affected organ. 
Very rarely an entire organ may 
become changed into a single 
tumor-mass. On a free epithe- 
lial surface and on mucous mem- 
branes a fibroma may appear in 
the form of a papilloma. 

According to the character of 
the connective tissue of which it 
is composed, the consistency of a 
fibroma may vary greatly. Often 
it is hard and tough, creaking un- 
der the knife (desmoid), and show- 
ing on its cut surface a white, tendon-like, shining tissue; but in other 
cases the growth may be soft, flaccid, the cut surface being more uni- 
formly grayish - white 
and somewhat translu- 
cent. In still other cases 
the individual strands 
of connective tissue are 
indeed white and shin- 
ing, but the tumor as a 
whole has a looser struc- 
ture and is correspond- 
ingly flaccid. 

Between the hard 
and soft growths there 
exist all possible transi- 
tion-forms, and even in 
one tumor different 
parts may possess dif- 
fer e n t characteristics. 
Under the microscope 

the hard kinds appear to be composed chiefly of thick bundles of coarse 
fibres (Fig. 239, a, b), in which lie scattered a larger or smaller number 
of cells. In the softer forms the bundles of fibres are more delicate 
(Fig. 240, a). If as a result of venous congestion or other cause a clear 




Fig. 240.— Section of an oedematous fibroma of the uterus (osmic 
acid, glycerin), a. Closely lying fibres; b, fibres pressed apart by 
fluid ; c, spindle-shaped cells ; d, swollen round cells ; e, blood- 
vessel. X 200. 



FIBROMA. 



381 



fluid collects between the fibrill^e, there is formed an oedematous fibroma, 
whose bundles of fibres (Fig. 240, h) are pressed apart by the fluid, the 
tissue becoming softer and more moist and translucent, and finally 
i-esembling the tissue of the umbilical cord. 

The soft forms of fibroma, which present a partly translucent, grayish- 
white cut surface, are usually very rich in cells ; so that it is possible 
by teasing to isolate numerous small spindle-shaped cells (nuclei with 




Fig. 241.— Fibroma pericauallculare mamuige (Miiller's fluid, alum carmine, eosin). a. Gland-tubules ; h, 
newly formed pericanalicular connective tissue rich in cells ; c, connective tissue poor in cells, x 35. 

tails). The intercellular substance is correspondingly less in amount, 
the fibrillse more delicate and arranged in finer bundles. Sections 
through such fibromata, when stained, appear very rich in nuclei (Fig. 
241, b). 

Fibromata develop from proliferating connective-tissue cells, and it 
is usually possible to find in the tumor certain areas which are richer in 
cells than the main mass of the tumor tissue, and in which the cells 
appear not only as small spindle cells, but also in part as round cells, or 
as short, thick spindles, or even as stellate cells. The transformation of 
the newly formed cellular tissue into connective tissue takes place in the 
same way as that described under Hyperplasia of Connective Tissue. A 
new-formation of elastic fibres is usually wanting, but at times such a 
new-formation does occur, particularly in the neighborhood of the blood- 
vessels. 

Fibromata may appear in any part of the body which contains any 
form whatsoever of connective tissue. They occur most frequently, for 
example, in the nerves, skin, periosteum, fascia, uterus, and mucous 
membrane of the nose ; more rarely in the ovary, mammary gland, intes- 
tinal tract, etc. In the mammary gland the development of the fibroma 
takes place particularly around the canaliculi (Fig. 241, &), so that the 
latter come to be surrounded by connective tissue rich in cells. 

Fibromata do not form metastases, but often occur as multiple 
tumors, especially in the nerves and skin (see ]N'eurofibroma, § 112). 



TUMORS. 



Moreover, it is not uncommon to see within a tumor several centres of 
growth — that is, the mass of the tumor is made up of several nodules or 
bands held together by ordinary connective tissue (Fig. 241, Fibro- 
mata are malignant only through their size and position. 

Fibromata may undergo fatty degeneration or may soften and disinte- 
grate, so that cavities may be formed within them. They may also break 
through and give rise to ulcers. Their blood -supply varies greatly, at 
times being scanty, at other times abundant. Occasionally the blood- 
vessels are ectatic, so that the tissue is intersi^ersed with wide channels 
and clefts, from which blood escapes when the tumor is examined in a 
fresh state. In other cases dilated lymph -channels are seen. 

Keloid is the designation applied to a hard, nodular, or flat and 
banded, or stellate growth of the skin, which in its fully developed state 
consists of dense fibrous tissue without elastic fibres. The direction of 
the fibres is often at right angles to the surface of the skin, or at least 
does not accord with that of the normal fibres. It usually develops after 
injuries or inflammations {cicatrix -keloid), but it may also appear without 
such association (spontaneous Jceloid). The cause of the keloid growth is 
not known ; the tendency to recurrence after removal, the multiple oc- 
currence, and the fact that many cases frequently occur in the same 
family (Hutchinson) speak in favor of a special predisposition on the 
part of the skin. 

Literature. 

(Fibroma and Keloid.) 

Aschoff: Gesclnvtilste. Ergebn. d. allg. Path., v., 1900. 
Jacobson; Keloid. Arch. f. klin. Chir., xxx., 1884. 

Jores- Elastische Fasern in Bindegewebsgeschwiilsten. Beitr. v. Ziegler, xxvii., 
1900, p. 389. 

Joseph: Ueber Keloide. Arch. f. Derm., 49 Ed., 1899. 
Jlirgens; Primare flerzgeschwiilste. Berl klin. Woch., 1891. 
Langhans: Keloid. Virch. Arch., 40 Bd., 1867. 
Lison: Sur la cheloide inguinale spontanee, Paris, 1887. 
Peterson: Ovarian Fibromata. American Gynaecology, 1902 (Lit.). 
V. Recklinghausen: Ueber die multiplen Fibrome der Haut, Berlin, 1882. 
Schiitz: Wahres Keloid combin. mit Narbenkeloid. Arch. f. Derm., 29 Bd.^ 1894, 
Thorn: Spontanes Keloid. Arch. f. klin. Chir., 51 Bd., 1895. 
TJnna: Die Histopathologic d. Hautkrankheiten, Berlin, 1894. 
Wilms; Pathogenese des Keloids. Beil^r. v. Bruns, 23 Bd., 1899. 
See also § 112. 

(b) Myxoma. 

§ 104. A myxoma is a tnmor Avliich consists essentially of mucous 
tissue, and is made up of cells and a fluid or gelatinous intercellular sub- 
stance containing mucin. The cells of the tumor are for the greater part 
polymorphous, with processes of varying length (Fig. 242) which anas- 
tomose with one another (Fig. 243, a). The tissue is markedly trans- 
lucent, soft, and the blood-vessels are easily seen through it. From the 
cut surface gelatinous masses or a stringy fluid, which swell up in Avater, 
may be obtained. 

No tumor is ever wholly made ui) of myxomatous tissue ; the latter 
is usually combined with other forms of tissue, particularly with flbrous 
connective tissue, fat tissue, cartilage, and sarcomatous tissne. For this 
reason such tumors are properly designated fibromyxoma, lipomyxoma 
(Fig. 245), chondromyxoma (Fig. 248, c), and myxosarcoma (Fig. 243). 



MYXOMA. 



383 



silicons tissue may develop from fibrous counective tissue through 
the collectiou of a muciu-coutainiug tiuid between the fibrillse and the 
gradual disappearance of the 
latter. Adipose tissue may 
j)ass over into myxomatous tis- 
sue through the disappearance 
of fat from the fat-cells and the 
appearance of a mucin -contain- 
ing gelatinous substance be- 
tween the cells, during which 
process the fat-drops become 
broken into swollen droplets 
(Fig. 245, b, c), while the cells 
themselves become smaller and 
star-shaped (d). Cartilage may 
also become transformed into 
mucous tissue through a mucoid 
degeneration of the basement- 
substance and a change of form 
of the cells (Fig. 248, c, d), 
Myxosarcomata (Fig. 243) arise 
either through a local increased 
activity of cell -proliferation in 
myxomata or through a collec- 
tion of mucoid substance be- 
tween the sarcoma cells. 

Myxomata, myxofibromata, and myxolipomata develop most fre- 
quently in the connective tissue of the periosteum, skin, heart, fascia, 
and sheaths ©f the muscles, as well as in the fat tissue of the subcuta- 




FIG. 24^ 



—Cells from a myxoma of the periosteum of 
the femur (gold preparation). X 40U. 




Fig. 243.— Section of a myxosarcoma (Miiller's fluid, carmine, glycerin), a. Myxomatous tissue ) b, strands 
of cells ; c, fibrous tissue. X 225. 



neous and subserous tissues and of the bone-marrow. Myxochondromata 
occur particularly in the parotid, and constitute the most common form 
of tumor found there. 



384 



TUMORS. 



These forms are all benign tumors, which rarely produce metastases. 
Myxosarcomata, on the other hand, have the characteristics of sarcomata 
and may form metastases. 

Literature. 

{Myxoma. ) 

Berthenson : Myxome de roreillette guaclie. Arch, de med. exp., 1893. 
Hertz: Myxom im rechten Seitenventrikel. Virch. Arch., 49 Bd., 1870. 
Heyfelder: Zur Resection des Oberkiefers. "Virch. Arch., 11 Bd., 1857. 
Jiirgens: Prhiiare Herzgeschwiilste. Berl. kliu. Woch., 1891. 

Koster: Myxom u. odemat. Bindegewebe. Sitzber. d. Niederrhein, Ges. f. Naturk., 
1881. 

Miiller, J.: Myxom. Arch. f. Anat. u. Phys., 1836. 

Orth: Schleim u. Schleimgeschwiilste. Ges. d. Wissensch. zu Gottingen, 1895. 

Robin: Myxome du coeur. Arch, de med. exp., 1893. 

Rumler: tie ber Myxom. Inaug.-Diss., Bonn, 1881. 

Virchow: Myxom. Yn'ch. Arch., 11 Bd. ; Geschwtilste, i., 1863. 

Wagner: CoUonema im Gehirn. Yirch. Arch., 8Bd., 1855. 

Weichselbaum: Myxom d. Oberschenkels m. secund. Knoten in d. Lunge. Yirch. 
Archiv, 54 Bd., i872. 

(c) Lijyoma. 

§ 105. A lipoma is a tumor consisting of adipose tissue (Fig. 244). 
These tumors are sometimes soft, sometimes firm, usually nodular and 
lobulated, and very often attain a very great size. In structure they 
are very similar to the subcutaneous adipose tissue — that is, they consist 
of fat-lobules held together by thick or narrow connective - tissue 
trabeculae. 

Histologically, the tissue of a lipoma resembles the fat-lobules of 
the subcutaneous panniculus (Fig. 244), although the tendency to form 
typical grape-like clusters of fat-cells is wanting. If, as not infrequently 

happens, mucous tissue is also 
formed in connection with the 
fat tissue, or if the latter, fol- 
lowing a disappearance of its 
fat, becomes changed into myxo- 
matous tissue, the tumor is des- 
ignated a lipomyxoma (Fig. 
245) ; if there is an abundance 
of fibrous tissue present, it is 
called a lipofibroma or fibroli= 
poma. 

Lipomata develop most com- 
monly from adipose tissue, but 
may arise also from connective 
tissue which normally contains no 
fat. Calcification, necrosis, gan- 

Fig. 244.— Lipoma of shoulder region, with relatively greue, and Sloughing are of not 

small fat-ceus (Miiiier's fluid, hajmatoxyiin) . X 300. infrequent occurrcuce in lipomata 

of large size. These tumors do 
not produce metastases, but are occasionally of multiple occurrence. A 
complete disappearance of a lipoma does not take place in the case of 
extreme general emaciation of the individual. 

Lipomata are sometimes observed even in new-born children — for 




LIPOMA. 385 

example, as tumors developing in or over the cleft-formations of spina 
bifida— but they occur much more frequently in later years. The )nost 
common seats of these growths are the subcutaneous tissues of the back, 




Fig. 245.— Lipomyxoma of the back (Miiller's fluid, Van Gieson's). a, Large fat-cells; b, c, fat-cells in 
which the fat is broken up into little droplets ; d, mucous tissue ; e, blood-vessel. X 300. 

buttocks, neck, axilla, abdomen, and thigh ; but they are found also in 
the intermuscular connective tissue, subserous fat tissue, in the kidneys, 
intestine, mammary gland, under the aponeurosis of the forehead, in 
the meninges, skin, fingers, lymph-glands, joints, etc. They may occur 
as multiple growths, and in such cases may be symmetrically distributed. 
In man there occurs a rare formation of fat tissue about the neck and 
throat, leading to nodular and lobulated disfigurations of the skin of this 
region, and giving occasion for the designation /a% collar (Madelung). 
The development of fat in these cases takes place partly in the subcuta- 
neous tissue, partly in and under the fascia and between the muscles. 
An abnormal develoi:)ment of fat in an extremity may give rise to a 
condition of lijyomafous elephantiasis. Should the process extend to the 
trunk and upper extremities, etc., conditions are established which re- 
semble very closely general obesity. 

Literature. 

(Lipo7)ia.) 

Adami: Retroperitoneal Lipoma. Mont. Med. Jour., 1897. 
Alveoli: La genesi del lipoma. Policlinico, 1900. 

Askanazy: Entsteh. multipler Liponie in Lj-mphdriisen. Virch. Archiv, 158 Bd., 
1899. 

Blaschko: Erbliche Lipombilduno-. Yiich. Arcli., 124 Bd., 1891. 
Brohl: Zur Aetiologie ii. Statistik der Li pome, Wiirzbiirg, 1886. 

Ehrmann: Multiple symmetrische Xanthelasmen ii. Lipome. Beitr. v. Bruns, iv., 
1888. 

Goebel: Ueber multiple Lipome. Cbl. f. allg. Patli., vi., 1895 (Lit.— Uebers). 
Grosch: Studien uber das Lipom. Dtsch. Zeitscbr. f. Chir., xxvi., 1887. 
Koettnitz: Symmetr. Auftreten der Lipome. Zeitscbr. f. Chir., 38 Bd., 1894. 
Langer: Multiple symmetrische Lipome. Arch. f. klin. Chir., 46 Bd., 1893. 



386 



TUMORS. 



Madelung- : Ueber den Fetthals. Langenbeck's Arch., xxxvii., 1888. 

Mestre : Essai sur le lipome, Montpellier, 1862. 

Mtiller: Lipome d. Nieren. Virch. Arch., 145 Bd., 1896. 

Steinheil: Ueber Lipome der Hand u. Finger. Beitr. v. Bruns, vii., 1891. 

Virchow: Die Krankhaften Geschwiilste, 1., 1863. 

Warthin: Fibrolipoma of the Kidney. Jour, of Path, and Bact., 1897. 

(d) Chondroma. 

§ 106. A chondroma or enchondroma is a tumor consisting essen- 
tially of cartilage. The amount of connective tissue taking part in the 
structure of the tumor, in part 




Fig. 246. FIG. 247. 



Fig. 246.— Periosteal chondroma of a digital phalanx, seen in longitudinal section, a. Chondroma; h, 
phalanx. Natural size. 

Fig. 247. — Section from a chondroma of the ribs (hematoxylin, carmine), a. Cartilage rich in small 
cells ; b, cariilage rich in large cells. X 80. 

its interior, is so slight as to fall completely into the background when 
compared with the cartilage. 

Chondromata develop chiefly in those places where cartilage is 
found normally — that is, in the osseous system or in the cartilages of 
the respiratory tract; but they also occur in tissues which normally 
possess no cartilage — for example, in the salivary glands, particularly in 
the parotid, and in the testicles, and more rarely in other organs. In 
the bones they develop from remains of cartilage which persist after ossi- 
fication, in the case of bones developing from cartilage ; but more often 
take their origin from the periosteum and bone-marrow (P^ig. 246). 
They form tumors which vary greatly in size. The small ones are usu- 
ally spherical (Fig. 246) ; the larger ones nodular or lobulated. The indi- 
vidual nodules are often separated from one another by connective tis- 
sue. ^N'ot infrequently they are multiple, particularly in the skeleton, 
and here again of most frequent occurrence in the hands and feet. 

The tissue of an enchondroma presents most often the characteristics 
of hyaline cartilage (Fig. 247), more rarely that of reticular or fibrous 
cartilage. At the periphery of the tumor the cartilage passes over into 
connective tissue, which forms a kind of perichondrium. 

The number, size, form, and grouping of the cartilage cells vary 
greatly in different cases and also in different parts of the same tumor. 
Many enchondromata are very cellular (Fig. 247), others poor in cells, 
many contain large cells, others small cells, or both large and small cells. 



CHONDROMA. 387 

The cells are sometimes surrounded by the so-called capsule, at other 
times not ; sometimes they lie in groups inside of the mother-capsule, at 
other times they are more 
regularly distributed. All 
the varieties of cartilage 
occurring normally in the 
organism are found in en- 
chondromata. Accord- 
ingly the cells vary in 
form, the majority show- 
ing the familiar sx)herical 
form, but spindle and stel- 
late cells are not rare, 
particularly in the neigh- 
borhood of the connective- 
tissue bands which divide 
the tumor into nodules or 
surround -it as a whole. 
Cartilage, the j)erichondri- 
um, bone-marrow, perios- 
teum, and different forms 
of connective tissue may 
form the matrix of enchon- 
dromata. Those arising 
from cartilage or bone are 
known as ecchondroses. 

The tissue of enchondromata very frequently suffers retrogressive 
metamorphoses. Very often a portion of the cells contain fat-droplets. 
The ground-substance in large tumors shows a tendency to undergo in 




Fig. 249.— Periosteal chondroma of the calcaneus, with areas of calcification (Miiller's fluid, haematoxylin). 
a, Hyaline cartilage ; c, calcified cartilage. X 225, 




Fig. 2i8.— Chondroinyxosarcouiaparotidis (alcohol, carmine), 
a. Cartilage ; h, sarcomatous tissue : c, myxomatous tissue ; d, 
cartilage in process of breaking down and being converted into 
sarcomatous and myxomatous tissue. X 80. 



388 



TUMORS. 



areas a mucoid degeneration and liquefaction. This may lead either to 
the formation of mucous tissue (Fig. 248, c), thus giving rise to a cho7i- 
dromyxoma ; or to a total liquefaction of the ground -substance with 
destruction of the cells, thus forming degeneratwn-cysis containing fluid. 




Fifi. 2o<J.- Osteochondroma of the hutiierus (alcohol, picric acid, hsematoxylin, carmine), a, Hyaline car- 
tilaa-t' : //. hone ; c, (.-arrilaore whicti is becoming' convertAri into bone ; (7, blood-vessel. X 250. 

In other cases the cartilage may become calcified (Fig. 249, h, c), or 
true bone may be formed (Fig 250, c, b), so that the tumor must be 
termed an osteochondroma. Through a marked proliferation of the 
cartilage cells sarcomatous tissue may be developed, the tumor becom- 
ing changed to a chondrosarcoma (Fig. 248, b). 

The enchondromata are, on the whole, benign tumors, although 
metastases may occur following a rupture into a lymph- or blood-vessel. 

In the region of the splieno-occipital suture, in the median line of the clivus, there 
is not infrequently found a small tumor which has been designated ecchondrosis phy= 
salifera sphenooccipitalis ( Vrrcltoic). It either lies beneath the dura, or at its high- 
est point breaks through this membrane and penetrates into the arachnoid and pia. In 
its typical form the tumor consists of bladder-like cells, resembling plant-cells; and 
takes its origin partly from the bone-marrow, partly from the surface of the bone. 
Cartilage and bone tissue maybe associated with the peculiar tumor tissue, and for this 
reason Virchotr regarded the growth as a chondroma arising from remains of the 
spheno-occipiral cartilage and characterized by a peculiar vacuolar degeneration of the 
cells. The peculiar character of the tissue, however, favors the view advanced by H. 
MuUer, and recently supported by Rihhert, that the growth is a product of a prolifera- 
tive activity of remains of the chorda {chordoma). 

Literature. 

(^Chondroma.) 

Beneke: Chondrom. Bibliothek d. med. "VTiss. v. Drasche, Wien, 1900. 
V. Biesiadecki: Metastasenbildung. Sitzungsber. d. Wiener Akad., Ivii. 
Birch-Hirschfeld: Zur Casuistik der Geschwulstembolie. Arch. d. Heilk,, x., 1869. 
V. Dembowski: Chondro-Endotheliome. Zeitschr. f. Chir., 33 Bd., 1891. 
Ernst: Unffew. Yerbreitung e. Knorpelgeschw. i. d. Blutbahn. Beitr. v. Ziegler. 
xxviii.,1900. 



OSTEOMA. 



389 



Prancois: Contrib. a I'et. d. renchondr. du bassin. These de Paris, 1876. 

Kast 11. V. Reckling-hausen : Ein Fall von Enchondrom mit ungewobnlichen Multi- 

plicationeu (Combination mit Cavernom). Yirch. Arch., 118 Bd., 1889. 
Klebs: Enchondrosis sphenooccipitalis amylacea. Virch. Arch., 31 Bd., 1864. 
Kiittner: Geschwulste d. Submaxillaris. Beitr. v. Bruns, xvi., 1896 (Lit.). 
Lesser: Enchondroma osteoides mixtum der Lunge. Yirch. Arch., 69 Bd., 1877. 
Nebelth.au: Gallertgeschw. d. Clivus Blumenbachi. Inaug.-Diss. , Marburg, 1897. 
Paget: Metastasenbilcfung. Med.-Ciiir. Transact., xxxviii., 1885. 
Ribbert: Ekchondrosis physalifera sphenooccipitalis. Cbl. f. allg. Path., v., 1894 

(Lit.); Exper. Erzeugung eiuer Ekchondrosis physalifera. Yerh. d. XIII. Congr. 

f. inn. Med., 1895. 
SctLlapfer, E.: Das Rippenchondrom, Leipzig, 1881. 
Steudel: Multiple Ekchondrome. Beitr. v. Bruns, viii., 1891. 

Virchow: Die krankh. Geschwulste, i., Berlin, 1863; Monatsber, d. K. Akad. d. 

Wiss. zu Berlin, 1875; Deutsche Klin., 1884. 
Volkmann: Endotheliale Geschwulste. Zeitschr. f. Chir., 41 Bd., 1897 (Lit). 
Wagner: Zur Casuistik des Enchondroms. Arch. d. Heilk., ii., 1861. 
Wartmann: Rech. sur renchondrome, Paris, 1880 (Lit.). 

Weber: Exostosen u. Enchondrosen, Bonn, 1856; Zur Geschichte d. Enchondroms, 
namentl. in Bez. auf heredit. Yorkommen u. secundiire Yerbreitung. Yirch. Arch., 
35 Bd., 1866. 

:Zeroni: Entwickelung d. Enchondroms d. Knochen. Arb. a. d. path. Inst, zu Got- 
tingen, 1893. 



(e) Osteo7na. 

§ 107. The term osteoma is applied to tumors which consist of osseous 
tissue. Such growths arise chiefly from the bones of the skeleton (Figs. 
251-253), but may develop elsewhere. 

The new-growths of bone arising in connection with the skeleton hav^e 
been variously designated according to their location and relations. A 
small circumscribed new-growth of bone attached to old bone is called 
an osteophyte ; when of a larger size and more tumor-like, an exostosis. 
Circumscribed formations of bone inside of bones are known as enostoses. 

attached to old bone are classed as follows: 
which have their seat in the periosteum but 



New-growths of bone not 
movable periosteal exostoses, 
are separated from the 
bone; parosteal osteomata, 
lying near the bone; dis- 
connected osteomata, which 
are situated some distance 
from the bone, in the 
muscles and tendons ; 
and, finally, heteroplastic 
osteomata, which occur in 
other organs, as, for ex- 
ample, in the lungs, mu- 
cous membrane of the 
trachea, in the skin, mam- 
ma, etc. 

Excrescences on the 
teeth, consisting of ce- 
ment - substance, are 
kndwn as dental osteo- 




ns 

mata ; those 



consisting of 



Fig. 351.— Ivory-like exostosis of the parietal bone. Natural size. 



dentine, as odoyitomata. 

According to their structure, osteomata may be divided into hard or 
ehurneous osteomata (osteoma durum or eburneum) (Figs. 251 and 253), 
and softer spongy forms {osteoma spongiosum or meduUare) (Figs. 252 and 
22 



390 



TUMORS. 





254). The former consist of firm, compact tissue like that of the 
cortical portion of the long bones, and possess ver^' narro\y nntrient 
canals (Fig. 253, a) ; the latter are made up of narrow, delicate bony 
trabecul?e and wide medullary spaces (Fig. 254), and resemble spongy 
bone in structure. 

The surface is sometimes regular and smooth, so that the whole tumor 
presents the form of a cone (Fig. 251), or of a sphere, or a pedunculated 
button; or it may be irregular, rough, and nodular, without definite 
resemblance to any given form (Fig. 252). The first variety occurs par- 
ticularly in the eburneous forms, which are found most frequently as 

exostoses upon the skull (Figs. 
251 and 253) ; the latter in the 
spongy exostoses and tlie dis- 
connected and heteroplastic 
osteomata, such as are found, 
for exami^le, in the falx of the 
dura mater (Fig. 254). 
/ Osteomata may occur as 

sinffle or midtiple tumors, the 
U latter mode of occurrence being 
relatively common. The ivory- 
' like exostoses of the cranium 

and the osteomata of the dura 
mater are very frequently of 
multiple occurrence, and circumscribed bony 
growths often appear in great numbers on 
the bones of the extremities and trunk. In 
such cases the epiphyseal ends of the bones 
and the points of insertion of tendons, or 
both at the same time, are the favorite seats 
of development. It is probable that such 
growths are to be referred to an inherited 
predisposition of the part affected to over- 
growth, or to disturbances in the development 
of the skeleton. At times a hereditary fac- 
tor can be demonstrated. The bony plates 
and spicules, which in rare cases develoj) in 
the lung or in the mucous membrane of the 
air-passages, may also occur in large numbers. 

The development of the bone takes place 
partly through the formation of osteoblasts, 
§ 84, and partly through metaplasia of formed tissues 



•I 



Fig. 252. — Exostosis cartilaormea 
of the upper diaphj^sis of the tibia. 
Reduced about one-half. 



as described in 



(§ 89). The matrix is formed chiefly from the connective tissue of tlie 
periosteum, as well as that of the tissue from which the osteoma arises ; 
and also from the cartilage and bone-marrow. If an exostosis devel- 
ops in such a manner that cartilage is first formed from the proliferat- 
ing periosteum or bone-marrow, and from this cartilage bone is later 
developed, it is called a cartilaginous exostosis (Fig 252) ; when the ex- 
ostosis is formed directly from the proliferating periosteum without an 
intermediate stage of cartilage, it is known as a connective-tissup exostosis 
(Figs. 251, 253, and 254). 

The combination of connective tissue and bone in a tumor, in such a 
manner that the connective tissue represents a chief constituent of the 
growth and does not simply represent the periosteum and bone -marrow 



OSTEOMA. 



391 



of the bone, gives rise To an osteofibroma. This is a very common 
timior of the osseous ^ystem. The abimdaut prodnctiou of boue in a 




Fig. 253.— Ivory-like osteoma <A the parietal bone, seen in fmiual >c-ction. a. Osteoma ; ?j, skull-cap. 

Eigbt-uiutbs natural size. 

chondroma leads to the formation of an osteochondroma i Figs. 250 and 
255) ; these tumors are likewise usnally fonnd in the long bones. The 




Fig. 264.— Osteoma of the dura mater (alcohol, picric acid, hsematoxylin. carmine) . X 40. 



392 



TUMORS. 



new -growth may develop in the periostenm (Fig. 255, c) or in the mar- 
row (fl, An abundant formation of bony trabeculte (/, A:) in the 
cartilage (e, i) gives to the tissue a firm, hard consistence. 

Many of the new-growths of bone which come under observation are 
not tumors in the strict sense of the term, but are hyperplasias resulting 
from excessive growth or from inflammatory i^rocesses. This is true 

particularly of man}- 
osteophytes and ex- 
ostoses, and also in 
part of the parostoses 
and the disconnected 
osteomata. The bony 
plates not infrequent- 
ly found in the falx 
of the dura, and 
which have a normal 
bone - marrow (Fig. 
254), are to be re- 
garded as misplaced 
portions of the skele- 
ton. The formations 
of bone known as 
rider^s hone and drill- 
hone , which are found 
in the adductors of 
the thigh and in the 
deltoid muscle, as the 
result of riding and 
the repeated shoulder- 
ing of arms, are to be 
regarded as tumors, 
which develop from 
a congenital anlage, in 
that the connective- 
tissue of the muscle 
shows characteristics 

which ordinarily belong only to the periosteum and bone-marrow. The 
so-called myositis ossificans — a peculiar disease of the muscles, character- 
ized by a j)rogressive ossification of their connective tissue during child- 
hood — is to be similarly interpreted. 





Fig. 355.— Osteochondroma of the humerus (alcohol, picric acid, hae- 
matdxylln, carmine), a, Cortical portion of the humerus: medul- 
lary ca%"ity ; c, periosteal deposit of bone ; (?. normal Haversian canals ; 
e, "dilated Haversian canals filled with cartila£:e, containing newly 
formed hone at f ; f/, cartilage with bone-trabeculte /(, formed by the 
periosteum ; i, cartilage with newly formed bone-trabeculge, arising 
from the marrow; /i, K old bone trabeculije ; remains of marrow- 
tissue. Pocket-lens magnification. 



Literature. 

{Osteoma.) 

Arnold, J.: Osteome der Stirnhohlen. Yircli. Arch., 57 Bd., 1873, 
Arnsperger: Knocbenbildung in der LuDge. Beitr. v. Ziegler. xxi., 1897. 
Benjamin;, Knochengeschwulst im Geliirn. Yircli. Arch., 14 Bd., 1858. 
Chiari: Multiple Exostosen. Prag. med. AYoch., 1892. 
Cohn: Diffuse Knochenbildung in der Lunge. Yirch. Arch., 101 Bd., 1885. 
Cohnheim : Multiple Exostosen. Yirch. Arch., 38 Bd., 1867. 

Dennig: Ueber Knochenbildung in der Trachealschleimhaut. Beitr. v. Ziegler, ii., 
1888. 

DeWitt: Myositis Ossificans. Amer. Jour, of Med. Sc., 1900 (Lit.). 
Ebstein: Osteom der 1. Kleinhirnhemisphare. Yirch. Arch., 49 Bd., 1870. 
Forster: Yerastigte Knochenbildung in der Lunge. Yirch. Arch., 18 Bd., 1858. 
Heuking-: Multiple Exostosen. Yirch. Arch., 77 Bd., 1879. 



HiEMANGIOMA AND LYMPHANGIOMA. 



393 



Heymann: Hercditare multiple Exostosen. Virch. Arch., 104 Bd., 1886. 
Huber: Multiple Exostosen. Virch. Arch., 88 Bd., 1882. 

Lenhossek: Knorpelahnliche u. wahre Knochenbildung im Penis, Virch. Arch., 60 
Bd., 1874. 

Meschede: Osteom des Grossliirns. Virch. Arch., 35 Bd., 1866. 

Mischnikoff: Knochenbildung in der Trachealschleimhaut. Inaug.-Diss., Zurich, 
1894. 

Neumann, E.: Osteom des Hodens. Arch. d. Heilk., 1875. 

V. Reckling-hausen: Ein Fall von multiplen Exostosen. Virch. Arch., 35 Bd., 1866. 
Reinecke: Erblichkeit multipler Wachsthumsexostosen. Beitr. v. Bruns, vii., 1891. 
Speng-ler: Ueber die Erblichkeit multipler Exostosen, Strassburg, 1887. 
Steudener: Osteome der Trachea. Virch. Arch., 42 Bd., 1868. 
Virchow: Die krankhaften Gescliwillste, ii., 1865. 
Weber, O. : Exostosen u. Enchondrome, Bonn, 1856. 

(/) Hcemangioma and Lymphangioma. 

§ 108. Under the term angioma are grouped those tumor -like forma- 
tions in the structure of which blood-vessels or lymph-vessels constitute such an 
important part as to determine the character of the tumor. 

Vascular tumors arising from blood-vessels are called hsemangiomata, 
or angiomata in the restricted sense of the term; those arising from 
lymph- vessels are designated lymphangiomata. Such tumors for the 
greater part represent formations which may be regarded as malforma- 
tions of a more or less extensive vascular area. Of the haemangiomata 
there may be distinguished four chief varieties: hcemangioma simplex, 
hcemangioma cavernosum, hcemangioma hypertrophicum, and angioma artericde 
racemosum. 

A hsemangioma simplex or teleangiectasia is a tissue-formation in 
which, within a ground tissue of normal occurrence in the body, there is 




Fig. 256.— Teleangiectasis of the panniculus adiposus of the abdominal wall (formalin, hsematoxylin, eosin). 
a. Blood-vessels filled with blood ; Z), adipose tissue. X 80. 



found an abnormal increase in the number or in the size of the capillaries and 
veins, whose structure iyi part is essentially changed. 

Such formations occur most frequently in the skin and subcutaneous 
tissue. They are usually congenital, but increase in size after birth. 
They are designated vascular nsevi, and are often found in places 



394 



TUMORS. 



where fetal clefts have closed (Jissuml anglomata). Of a tumor in the 
ordinary sense it is often scarcely iK)Ssible to speak, since the skin may 
show no tumor-like elevation. On the other liand, there occur extensive 




Fig. 257.— Dilated capillaries of a teleanffiectatic tumor of the brain, isolated from a portion of tumor by 

means of shaking. X 200. 

teleangiectases of the skin and subcutaneous tissue, presenting either as 
circumscribed growths or as flat, occasionally nodular thickenings of the 
skin, which may with propriety be termed tumors. The smooth ncevus 
vasculosus, on the other hand, ai^pears as an extensive superficial substitu- 
tion of the skin by another tissue. The color of the affected portion of 
the skin is either bright red (ncevus flmnmeus) or bluish-red (ncevus innosus). 
The line of demarcation between the normal and affected skin is usu- 
ally not a sharp one; 
around the edge and in 
the neighborhood of 
the chief area of dis- 
coloration there are 
often found little, cir- 
cumscribed red spots 
appearing as outrun- 
ners of the process. 

The red color is due 
to the dilated blood- 
vessels which are situ- 
ated either in the cor- 
ium or in the subcutaneous fat tissue (Fig. 256, a) ; and cases occur in 
which large areas of the subcutaneous adipose tissue present a red ap- 
pearance as a result of the pathological development of blood-vessels. 




Fig. 258.— Angioma cavernosum cutaneum congenitum (Miiller's 
fluid, haematoxylin). a. Epidermis; 7>, corium ; c, cavernous blood- 
spaces. X 20. 



HEMANGIOMA. 



395 



More rarely than in the skin and subcutaneous tissues, there occur sim- 
ilar angiomata in other places: in glands (mamma), bones, brain (Fig. 
257), and spinal cord and their membranes. Not infrequently, on the 
other hand, there are found analogous vascular changes in tumors, as, 
for example, in gliomata or sarcomata. 

If the vessels, which are usually abnormally abundant, are isolated, 
it becomes evident that the capillaries, or also the small veins {angioma 
simplex venosum), are more or less dilated. These dilatations (Fig. 
257) are either spindle-shaped or cylindrical, but may be saccular or 
spherical, and the different forms of dilatation may be combined in the 
greatest variety of ways. The dilated blood-vessels are united with 




Fig. 259.— Angioma cavernosum hepatis (Muller's fluid, haematoxylin, eosln). a, Liver tissue; b, angi- 

oma. X 100. 

each other by capillaries of normal size or of moderately increased cali- 
bre. The walls of the vessels are thin — that is, in comparison with nor- 
mal capillaries they are but slightly thickened. 

A hsemangioma cavernosum or tumor cavernosus is a vascular 
tumor consisting essentially of a cavernous spongy tissue, whose structure 
suggests that of the corpus cavernosum or spongiosum of the penis (Figs. 
244 and 245). Through the filling of the spaces with blood these tumors 
present a bluish-red or dark red color. 

The cavernous angioma, like the angioma simplex, occurs chiefly in 
the skin (Fig. 258, c) and subcutaneous tissues, where during the period 
of development it appears as a pathological formation of the vascular 
system. At times it forms only a small bluish-red spot {ncevus vasculosus 
vinosus) ; at other times, a smooth, elevated (Fig. 258), or slightly 
nodular bluish-red wart (ncevus vasculosus prominens, verruca vasculosa) ; 
or, finally, a circumscribed bluish-red discoloration or thickening of the 
skin. In the event of an extensive development of cavernous tissue in 
the subcutaneous or intermuscular connective tissue, there may result 



396 



TUMORS. 



large tiinwrs and ele2)h((ntiasis-Jil'e d/siiffu rat ions of portions of the hodif 
i^eJephantiasis hwmangiomatosa ) . 

Within the body the eaveruous angioma is found most commouly 
in the liver (Fig. 259, a, b), but may develop also in other organs: 




Fig. 2(30.— Ancrioma simplex liypertropliicum (formalin. liLFmat'wylin') . a, Vessels coataining blood; h, 
euiiny and rullaitsed Tliick-walit-d blood-ve<<eI< ricli in nuclei. X 100. 



kidney, s^^leen, intestine, bladder, bones, muscles, uterus, brain, etc. 
In the liver it appears in the form of dark-red areas, varying in size 
from that of a pin-head to several centimetres in diameter. They take 
the place of the liver tissue, and are not elevated, or but slightly, above 
the liver surface. 

The width of the blood spaces and the thickness of the trabecuhe 
vary greatly in different cases; the angioma may in portions or through- 
out be composed of fibrous tissue, 
in that more fibrous tissue was formed 
in the beginning, or fibrous prolifera- 
tious have taken place later as se- 
cpiehe To the thrombosis. The blood 
spaces are liued with endothelium; at 
times smooth muscle-fibres may be 
demonstrated in their walls, and the 
interstitial tissue is often rich in elas- 
tic fibres (Brilchanow). The tumor 
is usually sharply outlined from the 
neighboring structures by connective 
tissue. Usually no liver cells are 
fouiul in tlie trabecuhe. but varieties 
do occur in whii-li the latter in part 
enclose sucli. and in which, further, 
the blood spaces liere and there pass 
over into the liver-cai^illaries, such 
a communication ordinarily not taking place. 

The cavernous angioma of the liver occui s in old individuals, and also 
in infants and children of difierent ages, and not infrequently is of mul- 




FiG. 261.— Anei'ima simplex hvpertrophicum 
cutaneum et subcuTaneum (alcohol, carmine). 
In the middle >.f the section is the duct of a 
sweat-gland cut transversely. ■ 2oO. 



HEMANGIOMA. 



397 



tiple occnrreuce. It is probably caused by a local disturbance of de- 
velopment, which (Eibbert, Briichanow; proceeds from the vessels of 
Glissou'S cai)sule or from the intra-acinous capillaries (Orth, Schmieden) ; 
and is characterized by an abnormal development of the blood-vessels at 
the expense of the other tissues. The growth is slow and limited ; ordi- 
narih' the liver- cells in the immediate neighborhood show no signs of 
degeneration. During the period of rapid growth (Briichanow), there 
may occasional!}' be demonstrated in children the presence at the jyer- 
iphery of the growth of a cellular granulation tissue, in which the blood- 
vessels consist of delicate endothelial tubes of narrow lumen. 

The hsemangioma hypertrophicum, in its most typical form {lueman- 
gioma simxiJex liypertrophicum), occurs most frequently in the skin and 
subcutaneous tissues, where it forms circumscribed nodules similar in 
13art to the soft, smooth warts. The pathologically altered vessels may 
lie in the papillse and corium as well as in the subcutaneous tissue, and 
either form narrow tubes filled with blood (Figs. 260, «, and 261), the 




Fift. 262.— Angioma cavernosum hypertrophicum (an.aioendothelioma) of the sl^ull-cap (Miiller's fluid, 
haematoxylin). a. Blood-vessel with flattened endothelium; t>, blood-vessel with cubical and cylindrical 
endothehum. X 250. 

walls of which are more or less thickened and abnormally cellular, or 
else solid cords of cells (Fig. 260, h), which are either collapse.d, thick- 
walled vessels, or possess no lumen whatever. 

In very rare cases it happens that in angiomata, which from the cali- 
bre of the vessels bear the character of cavernous angiomata, there occurs 
a hypertrophy of the vessel- walls ; and this h^'pertrophy is due to the 
fact that the flat endothelial cells become changed into cubical and 
cylindrical cells (Fig. 262, h). Such a tumor may be classed as an 
angioma cavernosum Ju/pertroj)hicum, or as a Wood-vessel -endothelioma, or 
luemangioitic endothelioma; the last term being in particular applicable 
when, as a result of the marked proliferation and multiplication of the 
endothelium, there are produced nests of large cells which fill up the 
blood-vessels (compare EDdothelioma, g§ 115 and 116). 

A cirsoid aneurism, or angioma arteria'e racemosum, or angioma 
arteriale plexiforme (Fig. 26:3\ is a condition in which the arteries of 
an entire vascular area are dilated, tortuous, and thickened, so that there is 



898 TUMORS. 

formed a couvolntion of enlarged and thickened arteries. To the palpat- 
ing finger they feel like a bunch of earth-worms. Many of these angio- 
mata, which occur i)articularly upon the head, and which may cause 




Fig. 263.— Angioma arteriale plexiforme arterife ang-ularis et frontalis dext. et sin. 

erosion of the cranial bones, arise from congenital anlage ; others appear 
to be acquired, and develop after a traumatism, but it is possible that 
special conditions may have existed before the trauma. 

Literature. 

{Hcemangioma.) 

Appia: Des tumeurs sanguines erectiles, Paris, 1877. 

Beneke: Zur Genese der Leberangiome. Virch. Arch., 119 Bd., 1890. 

Bruchanow: Hamangiom der Leber. Zeit. f. Heilk., xx.. 1899. 

Burckhard: Pathol. Anat. d, cavernosen Angioms der Leber. luaug.-Diss., Wirrz- 
biirg. 1894. 

Dihbern: L^eber iinssere Angiome (Zusammenstellimg v. 95 Fallen), Kiel, 1869. 
Heine: Angioma art. racem. am Kopfe. Prag. Yierteljabrssdir., iii., iv., 1869. 
Hildebrandt: Ueber multiple caveruose Angiome. Deut. Zeitscbr. f. Cliir., 30 Bd., 
1889. 

Kretschmann : Ueber das Angioma arteriale racemosum, Halle, 1881. 
Langhans: Beitrage z. Lehre von den Gefassgeschwlilsten. Yirch. Arch., 75 Bd., 
1879. 

Markwald: Intra vasculares Endotheliom d. Knoclien. Yircli. Arch., 141 Bd., 1895. 



LYMPHANGIOMA. 



399 



Mauclair et de Bovis- Les angiomcs, Paris. 1896. 

Muscatello : Angiom der willkiirl Miiskeln. A^irch. Arch., 135 Bd., 1894. 
Nauwerck: Hyperplastisclies Capillarangiom. Yircli. Arch., Ill Bd., 1888. 
Pfeiffer. Ueber Teleaugiektasie u. cavernose Bliitgeschwulst, Tiibingeu, 1854. 
Reinbach- Zur Lehre v. d. Hamorrhoiden. Beitr. v. Brims, xix., 1897. 
Ribbert: Wachsthum u. Gcnese der Angiome. Virch. Arch., 151 Bd., 1898. 
Schmieden: Genese d. Lebercavernoms. Virch. Arch., 161 Bd., 1900. 
Schneck: Ueber d. Wesen u. d. Entsteliung des Angioma arteriale racemosum, Berlin, 
1885. 

Schrohe: Teleangiektasieen d. Leber Yirch. Arch., 151 Bd., 1898. 
Virchow: Die ls.rankhafteu Geschwlilste, iii. 

Wagner: Das arterielle Rankenangiom d. oberen Extremitaten. Beitr. v. Bruus, xi., 
1894 (Lit.). 

Weil: Beitriige zur Kenntniss der Angioma, Prag, 1877. 
See also § 116. 

§ 109. Angioma lymphaticum or lymphangioma is a tumor com- 
posed of a tissue the greater part of which is made up of dilated Jymph- 
vesseJs. The following different forms may be distinguished: lymphan- 
gioma simplex or teleanf/iectama lymplmtica (Fig. 264) ; lymphangioma 
cavernosum (Fig. 265); lymphangioma cystoides ; and lymphangioma hyper - 
trophicum. The cavities of these tumors usually contain a clear, liglit- 
coloi'ed lymph, but more rarely it is milky and contains mononuclear 
and j)olynuclear leucocytes, and usually also eosinophile cells. The 
walls consist of connective-tissue trabeculie of varying thickness and 
containing more or less involuntary muscle ; the spaces are lined with 
eiidothelium. 

In the lymphangioma simplex (Fig. 264) the lymph-vessels of a 
more or less extensi\'e area are dilated and their w alls for the greater 
part are thickened. In the cavernous lymphangiomata the number of 




FiCt. 264.— Weeping subepithelial lymphangioma of the skin (alcohol, carmine), a, Corium ; h, epithelium 

c, d, lymph-spaces. X 14. 



lymi^h-vessels is still greater, their spaces are larger, and the intervening 
tissue is less abundant, so that, even to the naked eye, the tissue presents 
a spongy ai)pearance. The cystoid lymphangiomata contain cysts vary- 
ing in size from that of a pea to a w^alnut. The tissue between the 
dilated lymph-vessels consists, according to the location of the tumor, 
either of connective tissue (Fig. 264), fat tissue (Fig. 265, c), muscle, or 
some other tissue. At times nodes of lymphadenoid tissue may be en- 
closed (e), and may present evidences of active proliferation. 



400 



TUMORS. 



Lymphaugiomata are sometimes congenital ; at other times they make 
their first appearance at a later period of life. 

The congenital forms occnr particularly as different varieties of 
ectasia of lymph -vessels, and are found chiefly in the tongue (macro- 
glossia), palatal arch, lips (maovcheilia), skin (ncevus lymphaticus) , sub- 
cutaneous tissue, in the neck {hygroma colli congenitum), vulva, etc. The 
lymphangiomata of the skiyi spread over more or less extensive areas of 
the skin, and form either smooth or irregular elevations of the same. If 
the blood-vessels are numerous the growth may have a red color. The 
rupture of dilated lymi)h-vessels lying immediately beneath the epithe- 
lium (Fig. 264, (7) may give rise to a moist condition of the surface and 




Fig, 26.5.— Lvmphansioma oavernosiim subcntaneum (alcohol, alum-carmine), a, Ectatic Ivmph-vessels; 
b, connective tissue ; c, aaipose tissue ; d, large blood-vessels ; c, cellular areas, x 20i). 



eventually to a lymphorrhoea. The extension of the cavernous develop- 
ment of the lymph-vessels over large areas of the skin and subcutaneous 
tissue may give rise to elephantiasis-li'ke disfigurations of the part affected, 
^^"ot infrequently the intervening connective tissue also takes part in the 
hypertrophic growth, or there develoiDS a fibrous elephantiasis in connec- 
tion with lymphangiectasia. 

In rare cases chyle-containing growths (chyJangiomata) are found in 
the intestinal wall or mesentery. Cystic lymphangiomata are also found 
rarely in the peritoneum. 

The pathological formations which may be classed as hypertrophic 
lymphangiomata represent peculiar changes of the skin, which ai^e 
either congenital or develop in early youth. They are commonly known 
as pigmented moles, lentigiues, freckles, and fleshy warts. 

ThOi pigmented moles, oy nceri pigmentosi, ov melanornata, form lai ger or 
smaller smooth areas which are not elevated above the general surface of 
the skin (ncevus spilns), or prominent warty growths (ncevus prominens, 
ncevus verrucosus). When covered with hair, as i;> frequently the case, 
they are called hairy moles (ncevus jiiJosus). In color they are usually 
light brown or dark brown, or even black (Fig. 266) ; and are usually 



LYMPHANGIOMA. 



401 



covered by epidermis of normal thick- 
ness, more rarely by hypertrophic epi- 
tlielium. They are nsually small, bnt 
may be as large as the palm of the hand, 
or nnder certain conditions may cover a 
hu ge i)ai't of the body surface. 

Lviitlglnes appear at any time after 
birth, and ni)on any part of the body 
surface ; and when once formed they re- 
main for life. They form shar^^ly cir- 
cumscribed yellow to brownish - black 
spots closely resembling the little pig- 
mented ngevi ; and vary in size from that 
of a i:>inhead to that of a lentil. 

FreeMes or ephelides are small, irregu- 
larly outlined, serrated, pale-brown spots, 
which are not elevated above the surface 
of the skin. They occur in young indi- 
viduals, i)articularly on the face, hands, 
and arms,, rarely on other x^ortions of the 
body ; and may either remain permanently 
or disappear after a longer or shorter 
time. The pigmentation is favored by 
exposure to sunlight. 

Fleshy moles (vei^rucce carnew) are non- 
jngmented, circumscribed, smooth (Fig. 
2(37) or slightly irregular, or more rough 
and i^apillary (Fig. 269) i^rominences of 
the skin, over which the epidermis is at 
times normal, at other times somewhat 
hypertrophic (Fig. 269, «)• 

In all of the pathological formations 
just described the connective-tissue frame- 
work encloses coUeetions of cells, either in round or cord-like masses 
(Figs. 267, 268, 269, d, d^, which lie partly in the papillae and partly 
in the corium; and are the more abundant the more the growth pro- 




FiG. 2('G. — Large liairy and pigmented 
nieviis of back, buttocks, and thighs, with 
scattered smaller pigmented spots over the 
remaining portions of the body. (After 
Rohring.) (Reduced from original.) 




Fig. 267.— Lymphangioma hypertrophicum. Section through a small, soft, smooth wart (formalin, haema- 

toxylin, eosin). X 40. 



402 



TUMORS. 




Fig. 268.— Lympbangioma hypertrophicum. Rounded summit of a largre, soft, smooth wart (formalin, 
ha?matoxylin, eosin). Sharply outlined cell-nest incoriuui. x 250. 

jects above the surface of the skin. In the pigmented forms the cells 
of the cell -nests may also contain the pigment (chiefly in the form of 
brown or yellow granules, but in part diffused throughout the substance 




Fig. 269.— Section through two papillae of a papillary fleshy wart (alcohol, carmine), a, Thickcued 
horny layer of the epidermis; //, epitheliaJ pearls; c, rete Malpighii ; c/, neste and strands of cells in the 
papilliE ; c?i, nests and strands of cells in the reticular layer ; c, connective tissue. X 50. 



LYMPHANGIOMA. 



403 



of the cells) ; though often the pigment lies chiefly within the connec- 
tive tissue cells of the tibrons portions of the growth. 

Tlie cells of the cell-nesls are relatively large (Fig. 268), possess an 
abundant protoplasm, and a bright, bladder-like nucleus. Their posi- 
tion and appearance justify the assumption that they represent the prod- 
ucts of the jjroliferation of the endothelial cells of the lymph-vessels. In 
rarer cases similar formations arise from the blood-vessels (hsemangioma 
hypertrophicum). Accordingly, it would seem proper to class these 
growths with the endotheliomata or lymphangiosarcomata, but their lim- 
ited growth makes their classification as lymphangiomata more appro- 
priate (see § 115). The cell-nests of the hypertrophic lymphangioma 
may in part spread out more diffusely through the tissues (as is the case 
with the hyj)ertrophic hsemangioma), so that the peculiar structure of 
the growth may be lost. In rare cases there may develop a combination 
of hyj)ertrophic lymphangioma and lii^oma. 

JJnna, Kromayer, Delhanco, and Marchand held the view that the cell-nests of the 
cellular ncevi are of epithelial origin, and represent misplaced portions of the surface 
epithelium ; and Kromayer goes so far as to assume a metaplasia of epithelium into 
connective tissue. Preparations showing the first stages of the development of na^vi 
are not accessible to me; but a thorough study of ntevi and fleshy warts of a later stage 
does not show any connection between the cell-nests and the epithelium ; and conse- 
quently I hold the opinion — notwithstanding the investigations of the above-named 
authors — that the view given above in the text, in regard to these na^vi and fleshy 
warts, harmonizes most perfectly with their anatomical nature and clinical behavior, 
both in their fully developed condition as well as when they undergo a transformation 
into malignant sarcomata. That in individual cases the cell-nests lie close to the epi- 
thelium is no proof of a genetic relationship, since the ordinary lymphangiomata also 
lie close to the epithelium (Fig. 264, d). 

Literature. 

{Lymphangioma and Celhdar Ncevi. ) 

Arnold: Zwei Fitlle von Hygroma colli congenitum. Virch. Arch., 32 Bd., 1865. 
Arnstein: Zur Casuistik der Makroglossie. Virch. Arch., 54 Bd., 1872. 
Bauer: Endotheliale Naevi. Virch. Arch., 142 Bd., 1896. 

Bayer: Bedeut. d. Fettgevvebes f. d. Aufbau d. lymphat. Neubildungen. Zeit. f. 

Heilk., xii., 1891. 
V. Biesiadecki: Untersuch. aus dem pathol. Institut., 1872. 

Bircher: Aetiol. d. Naevus pilosus (uutergegangenes Zwillingsgeschwister). Arch. f. 

Derm., 41 Bd., 1897. 
Bog-oliubsky : Die Pigmentflecken der Haut. Inaug.-Diss., Bern, 1887. 
Delbanco: Epitlielialer Naevus. Monatsh. f. prakt. Derm., xxii., 1896. 
Demieville: Ueber Pigmentflecken der Haut. Virch. Arch., 81 Bd., 1880. 
Freudweiler: Lymphang. cystoides cutis. Arch. f. Derm., 41 Bd., 1897. 
Frobenius : Ueber einige angeb. Cystengescliwiilste des Halses. Beitr. v. Ziegler, vi. , 

1889. 

Gaucher et Lacapere : Lymphangiome circonscrit. Arch, de med. exp., 1900. 
Hebra u. Kaposi: Handb. d. Hautkrankh., ii., 1872. 

Koster: Ueb. Hygroma colli congenitum. Verb. d. Wiirzb. pliys.-med. Ges., iii., 
1872. 

Kromayer: Histogenese d. weichen Hautnaevi. Derm. Zeitschr., 1896; Erwiderung 

an Ribbert. Beitr. v. Ziegler, xxii. ,'1897. 
Kruse: Ueber das Chylangioma cavernosum. Virch. Arch., 125 Bd., 1891. 
Kiittner: Intermittir. Entziindung d. Lymphangiome. Beitr. v Bruns, xviii., 1897. 
Langhans; Lymphangiom d. unt. Extremitat. Virch. Arch., 75 Bd., 1875. 
Lesser u. Beneke: Lymphangioma tuberosum multiplex. Virch, Arch., 123 Bd., 

V. Lesser: Lymphangioma diffusum multiplex. Zeitschr. f. Chir., 34 Bd., 1893. 
Lion: Lymphcysten d. Ligam. uteri latum. Virch. Arch., 144 Bd., 1896 (Lit.). 
Loewenbach: Histogenese der weichen Naevi. Virch. Arch., 157 Bd., 1899. 
Nasse: Ueber Lymphangiome. Langenbeck's Arch., 34 Bd., 1887. 



404 



TUMORS. 



zurNieden: Lymphangiektasie mil Lymphorrhagie. Vircli. Arch., 90 Bd., 1882. 
Pinner: Lympliangiom. Cbl. f. Cliir., 1880. 

V. Planner: ISIaevus congenitus. Vierteljahrssclir. f. Derm. u. Sypli., xiv., 1887. 
V. Recklinghausen: Die niultiplen Fibrome der Haut, Berlin, 1882. 
Reichel: Augeb. Lymphangioma cysticum. Virch. Arch., 46 Bd., 1869. 
Ribbert: Waclisthum u. Genese d. Angiome. Virch. Arch., 151 Bd., 1898. 
Ritschl: Lj^mphangiome d. Miiskeln. Beitr. v. Brvms, xv., 1895. 
Roth: Retroperitoneales cystisches Lymphangioma, Zurich, 1880. 
Sachs: Lymphangioma am Auge. Beitr. v. Ziegler, v., 1889. 

Samter: Ueber Lymphangiome der Mundliohle. Langenbeck's Arch., 41 Bd., 1891. 
Schmidt: Beitr, z. Kenntniss d. Lymphangiome. Arch. f. Derm., xxii., 1890. 
Schultes: Diffuse Lymphangiombildung am Oberschenkel. Inaug.-Diss., Freiburg, 
1894. 

Steudener: Cavernoses Lymphangiom der Conjunctiva. Virch. Arch., 59 Bd., 1874. 
Stiles : Rep. of a Case of Cavernous Lymphangioma of the Forearm. Edinb. Hosp. 
Rep., i., 1893. 

TJnna: Naeviu. Naevocarcinome. Berl. Idin. Woch., 1893; Virch, Arch., 143 Bd., 1896. 
Variot: Note s. 1. les. de la peau dans la melanodermie congen. Arch, de phys., x., 
1887. 

Virchow: Die krankh. Geschw., iii. ; Hvgroma cysticum glutaeale congen. Virch. 
Arch., 102 Bd. 

Waelsch: Lymphangioma cutis cysticum. Arch. f. Derm., 51 Bd., 1900. 
Wegner: Ueber Lymphangiome. Arch. f. klin. Chir. v. Langenbeck, xx., 1877. 
Weichselbaum : Cliylangioma cavernosum des Mesenteriums. Virch. Arch., 64 Bd,, 
1875, 

(g) Myoma. 

§110. A myoma is a tumor cousistiiig essentially of neivly formed 
muscle-fibres. AccordiDg to the nature of the muscular elements, mj^o- 
mata are divided into leiomyomata formed of unstriped muscle, and rhcibdo- 
myomata composed of striped muscle. 

The leiomyoma, or myoma Iwvicellulare, occurs most frequently in the 
uterus, more rarely in the tubes, uterine ligaments, labia majora, mus- 




FiG. 270.— Myoma of the uterus (Miiller's fluid, haematoxylin, eosin). X 300. 



cularis of the gastro- intestinal tract and urinary passages ; and may form 
spherical, nodular tumors of varying size. In rare cases it is found also 
in the skin and subcutaneous tissues, forming in this location small 



MYOMA. 



405 



nodules occasionally reaching the size of a pigeon's egg. Leiomyomata 
occur as eithei- single or multiple tumors; and may appear during child- 
hood, or even develop under certain conditions during intrauterine life 
(Marc). 

In muscular organs the new-growth proceeds from the muscularis, 
and forms during its development bundles of muscle-fibres (Fig. 270) 
which are interwoven in different directions, and consequently present 




Fig. 271.— Angiomyoma subcutaneum dorsi (alcohol, haematoxylln, eosln). a, Cavernous blood-ves- 
sels ; t), strands of muscle cut longitudinally ; c, same cut transversely ; d, cannective tissue ; e, artery 
with hypertrophic muscularis ; /, groups of lymphoid cells. X 46. 



in sections a variety of pictures according to the directions in which the 
bundles are cut. Myomata of the uterus may contain included uterine 
glands. Those developing iu the dorsal wall of the body of the uterus 
and near the angles of the tubes, or in the inguinal region, may contain 
a varying number of gland-tubules which arise from the Wolffian body 
(von Eecklinghausen) ; such tumors may be designated adenomyomata. 
They are distinguished from the ordinary spherical myomata which are 
sharply circumscribed, by the fact that their boundaries are not sharply 
defined. Eventually some of the glands may become cystic as the result 
of the accumulation of secretions. According to Eicker, Pfannenstiel, 
and others, the ordinary uterine myomata as well as those of the vaginal 
vault may also contain epithelial tubes, which probably owe their origin 
to inclusions of portions of the duct of Miiller. In the skin and subcu- 
taneous tissue the new-formation of muscle-fibres proceeds in the first 
place from the muscularis of the vessels (Fig. 271), which thereby be- 
come thickened (a), and at the same time give rise to free strands of 
muscle-fibres (b). A pathological new-formation of blood-vessels may be 
associated with that of muscle (a), so that tumors arise which are desig- 
nated a^^^^om2/omato (Fig. 271). According to observations by Jadassohn 
23 



TUMORS. 



iiud others, multiple luyoiiiata of the skin may take tlieir oi igiii either 
from the arreetores pilorum or from the musele-cells of tlu^ sweat-glands. 

A certain amonnt of connective tissue always takes part in tlie for- 
matiou of a myoma, and often assumes such inipoitance that tlie tumor 
may with propriety be called a fibromyoma or myofibroma. For 
example, the inajority of the uterine myomata aie tibromyomata. The 
fibrous connective- tissue portions of the tumor appear glistening white, 
the mnscular i3ortions more reddish-wliite or clear reddish-gray. The 
spindle-shaped muscle-hbres may be isolated by teasing a bit of the 
tumor or by maceration of the same for twenty-four hours in a twenty- 
per-ceut nitric-acid solution or for twenty to thirty minutes in a thirty- 
four-x^er-cent solution of i^otassium hydroxide. In longitudinal sections 
the muscle-fibres are most easily recognized by their rod-shaped nuclei 
(Figs. 270, 271), as well as by the regular structui e of the cells in bands 
or strands. In cross-section the muscle-cells ai^pear as small flattened 
cells containing in their centres the transversely cut nuclei (Fig. 270). 

The leiomyomata are benign tumors, but often reach a very large size, 
and sometimes undergo a sarcomatous proliferation. In fibromyoniata of 
the uterus there not infrequently occur fatty degeneration and softening, 
which may lead to the disintegration of the growth or to the formation 
of cystic cavities. Calcification may also occur. Through degeneration 
and atrophy of the muscle fibres a myofibroma may become transformed 
into a fibroma. 

A rhabdomyoma (Zenker), or myoma strioceUidat-e, is on the whole 
a rare tumor. Its most characteristic feature is the presence of stri- 
ated muscle-fibres, which in part are fully developed and in part un- 




FiG. 272.— Cells from a rhabdomyoma. (After Ribbert and Wolfensberger.) a, b, c, d. Striated fibres 
of varying thickness ; d, small nucleated fibre without striation : e, spindle-cell with longitudinal striation ; 
/, spindle-cells with longitudinal and transverse striation ; (/, spindle-cells, wnthout striation, with elon- 
gated processes ; h, i, round (*ells with concentric and radial striation. 



develoi^ed. When Avell developed the muscle-fibres form multinuclear 
bands of varying width, which present a cross-striation (Fig. 272, a, b, 
c), and in part also a longitudinal striation (e,f). The undeveloped 
forms consist of narrow bands without transverse striations (d) ; of 
spindle-cells with long-drawn-out thread-like processes without transverse 
striation (g) or with partial striation (/) ; or, further, of round cells of 



MYOMA. 



407 



different sizes, which present eitlier a radial or a concentric fibrillation 
01' striation (/?, /). Besides these there are aLso cells which possess no 
especial characteristics, so that it is impossible to decide whether they 
are young iindeveloiied muscle-cells or connective-tissue cells. The 
bands as well as the spindles are usually arranged in interlacing bundles. 
It is usually not possible to demonstrate with certainty the presence of a 
sarcolemma on the sui'face of the fibres ; but various delicate membranes 
have been described by different authors, which probably are to be re- 
garded as representing i^ortions of a sarcolemma. 

Ehabdomyomata of the heart, in so far as they do not consist of a 
formation of delicate transversely striated muscle-fibres, are made up of 
a delicate network supported by connective -tissue bands, in the clear 
spaces of which network there lie spider-like cells, whose processes are 
partly free, and partly continuous with the reticulum. According to 
Seiffert, these cells are to be regarded as enlarged embryonal muscle- 
cells, which, in the event of an overproduction of the structureless pro- 
toplasmic portion, have formed no transversely striated covering. 

Ehabdomyomata occur most frequently in the kidney or its pelvis, 
in the testicles, and uterus ; more rarely iu other regions, as, for exam- 
ple, in the vagina, bladder, muscles, heart, nerves, subcutaneous tissue, 
mediastinum, oesophagus, etc., and form nodular, or, in case they are 
situated on the surface of a mucous membrane, papillomatous and poly- 
poid tumors, which vary greatly in size. They develop from striped 
muscle, possibly also from smooth muscle (uterus). In the kidneys and 
testicles they either form circumscribed nodules, or lead to a total 
destruction of the organ. The origin of the tumor in these cases is prob- 
ably from misplaced anlage of muscle-tissue; and accordingly suck 
growths are most frequently congenital. They may, however, develop 
first at an advanced age. Occasionally they enclose other tissues, for 
example, cartilage. Moreover, muscle-fibres of corresponding stages of 
development occur in the complex tumors of the testicles and kidneys 
(see Teratoma). 

If a tumor contains only a few cells which can be definitely recog- 
nized as muscle-fibres, while the majority of the cells have no specific 
character, the tumor is ordinarily designated a rliahdomyosarcoma. 

Literature. 

{Leiomyoma and JRhabdomyoma . ) 

Arnold: Glj^kogenhaltiges Mvoma striocelhilare des Hodens. Beitr. v. Zie2:ler, viii., 
1890. 

Becker; Muskelgeschwiilste des Hodeus. Virch. Arch., 163 Bd., 1901. 
Brodowski: Myosarkom des Magens. Virch. Arch., 67 Bd., 1876. 
Cesaris-Demel : Rabdomioma del cuore. Arch, per le Sc. Med., xix., 1895 (Lit.). 
Cohen: Histogenese der Myome. Virch. Arch., 158 Bd., 1899. 

Cohnheim: Congenitales qnevgestreiftes Mnskelsarkom der Nierc, Virch. Arch., 65 
Bd..l875. 

Eberth: Myoma sarcomatodes renum. Virch. Arch., 55 Bd., 1872. 
Fujinami: Rhabdomyosarkom im Muskel. Virch. Arch., 160 Bd., 1900. 
Gebhard: Myome d. Uterus. Handb. v. Veit, ii., Wiesbaden, 1897 (Lit.). 
Helbing: Rhabdomyom an Stelle der ]. Lunge. Cbl. f. allg. Path., ix., 1898. 
Herzog: Cutaneous Myoma. Journ. of Cutau. and Geuito-urin'ary Dis., 1897 (Lit.). 
Hess: Ein Fall von multiplen Dermatomyomen an der Nase. Virch. Arch., 120 Bd., 
1890. 

Huber u. Bostrom: Myosarkom der Niere. Deut. Arcli. f. klin. Med., 23 Bd. 
Jadassohn: Zur Kenntniss der multiplen Myome der Haut. Virch. Arch., 121 Bd., 
1890. 



408 



TUMORS. 



Kunze; Zur Casnistik der Myome ties Mugens. Arcli. f. klin. Chii-., 40 Bd., 1890. 
Lartig-au and Liarkin: Multiple Leiomyoniata of the Kidney. Joiirn. of Med. Res., 
1901. 

Lukasiewicz: Multiple Dermatomyome. Arch. f. Derm., xxiv., 1892. 
Marc: Leiomyoma subcutaneum congenitum. Virch. Arch., 125 Bd., 1891. 
Marchand: Myosarcoma striocellulare der Niere. Yirch. Arch., 73 Bd., 1878; Ueber 

eine Geschwulst mit quergestreiften Muskelfasern. lb., 100 Bd., 1885. 
Neumann: Myoma striocellulare des Hodens. Virch. Arch., 103 Bd., 1886; Multiple 

Dermatomyome. Arch. f. Derm., 39 Bd., 1897. 
Orlandi: Rabdomioma del nervo ischiadico. Arch, per le Sc. Med., xix., 1895 (Lit.). 
Paviot et Berard: Cancer musculaire lisse (maligne Myome). Arch, de med. exp., 

1897. 

Pernice: Myosarcoma striocellulare des Uterus. Virch. Arch., 113 Bd., 1888. 
Prudden: Rliabdomyom d. Parotis. Amer. Jour, of tlie Med. Sciences, April, 1883. 
V. Recklinghausen : Die Adenomyome u. Cystadenome des Uterus, Berlin, 189G. 
Ribbert; Myosarcoma striocellulare des Nierenbeckens. Virch. Arch., 106 Bd.: Zur 

Kenntn. der Rhabdomyome. lb., 130 Bd., 1892. 
Ricker: Aetiologie der L^^terusgeschwulste. Virch. Arch., 142 Bd., 1895. 
Seiffert: Multiple Rhabdomyome des Herzens. Beitr. v. Ziegler, xxvii., 1900. - 
Smith.: Fibromyomatous Tumors of the Vagina. Amer, Journ, of Obst., 1902. 
Steiner: Myome d. Magendarmkanaies. Beitr> v. Bruns, xxii., 1898 (Lit.). 
Tusini; Rabdomioangioma del dorso. Arch, per le Sc. Med., xx., 1896. 
Virchow: Die krankhaften Gescliwiilste, iii., 1865. 

Williams: Histogenese d. Uterussarkome (Myoma sarcomatodes). Zeitschr. f. Heilk., 
XV., 1894. 

Wolfensberger : Rhabdomyem der Speiserohre. Beitr. v. Ziegler, xv., 1894. 
Zenker, K. : Rhabdomyosarkom der Orbita. Virch. Arch., 120 Bd., 1890. 



(h) Glioma and Newoglioma Ganglionar e. 



§ 111. A glioma is a tumor which develops from the cells of the sup- 
jportiilg tissue of tJie central nervous system (neuroglia), and in its fully 

developed condition consists essentially of 
these cells. In the brain the gliomata form 
tumors, which for the most part are not 
sharply defined from the normal brain-sub- 
stance, but pass into the 
latter by insensible gra- 
dations. At times they 
appear simply as local 
swellings of the brain, 
and only the difference in 
color and the disappear- 
ance of the normal tissue- 
contrasts between the dif- 
ferent elements of the 
brain, give evidence to 
the eye that a tumor is 
present. In the spinal 
cord they arise most fre- 
quently in the neighbor- 
hood of the central canal, 
and may extend over a 
large portion of the cord. 
Their appearance varies greatly; sometimes they are light-gray, 
somewhat translucent, and similar in color to that of the cortex, and 
moderately firm in consistence ,* at other times they are more grayish- 
white, denser, and firmer; and again they are not infrequently grayish- 
red or dark red in color. In the last case they are traversed by numerous 





Fig. 373.— Glioma cerebri. A, Cells Isolated by teasing and 
stained with carmine. B, Section from same glioma after harden- 
ing in Miiller's fluid (Bismarck brown). X 350. 



GLIOMA AND NEUROGLIOMA. 



409 




Fig. 274.— Section of a glioma of the cerebrum, 
with astrocytes (xMiiller's fluid, hii?matoxylin, 
Mallorv's method.) x 500. 



The ganglion-cells 
Within the tnmor 



large vessels. Gliomata well supplied with blood often contain haemor- 
rhagic areas. Fatty degeneration, softening, and destruction of the tissue 
are also of common occurrence. 

A section of a fully developed glioma shows under the microscope a 
network of extremely delicate glistening fibrillse (Fig. 273, B), in which 
are imbedded numerous short oval nuclei. About the nuclei there is 
but a scanty amount of protoplasm, and this can be distinguished only 
with difficulty. When examined in the fresh state or after maceration 
in Miiller's fluid it may be seen dis- 
tinctly that these nuclei belong to 
cells (astrocytes) which are charac- 
terized by a great number of fine 
processes extending in all directions, 
and often branching (Fig. 273, A). 
By x^roper staining-methods the con- 
nection between some of the fibres 
ma}^ be demonstrated also in sections 
(Fig. 274). 

The cells are very similar to nor- 
mal glia-cells; but are not infre- 
quently much larger, occasionally 
more plumj^, and some may possess 
two, three, or four nuclei. 

Investigations as to the develox)- 
ment of gliomata have proved that 
the glia-cells are the mother-cells of the tumor-cells, 
do not take any j^art in the proliferative process, 
there may be found cavities lined Avith epeudyma-epithelium (Stroebe), 
and this may be regarded as e\'idence of their connection with some dis- 
turbance of develox^ment of the brain or spinal cord. The number of 
cells in a glioma varies greatly. At times the cells greatly predominate, 
at other times the fibrillge. A simultaneous proliferation of the cells of 
the perivascular connective tissue leads to the formation of giiosarcomata. 

The glioma usually occurs singly, and does not produce metastases. 
Traumatism may furnish the exciting cause for its develoi^ment. 

The term glioma is also applied to certain tumors of the retina occur- 
ring during childhood. These growths, a certain portion of which are 
of congenital origin, are evidently to l)e lef erred to some disturbance in 
the development of the retina. They foi m cellular, soft, white or reddish 
tumors, the greater part of which consists of small, round or irregular 
cells poor in protoplasm, resembling the cells of the stratum granulosnm. 
In pai't they possess smaller or larger processes. These cells are found 
best preserved in the neighborhood of the blood-vessels, while in other 
portions of the tumor they often show retrograde clianges. The tumor 
may also contain ganglion-cells, cylindrical cells, and peculiar rosette 
and ribbon-like cell-formations (Wintersteiner), these latter being re- 
garded as aggregations of rods and cones. Wintersteiner has, therefore, 
designated the tumor a neiiroepithelioma. 

The glioma of the retina often shows areas of necrosis in its central 
portion. In its gi'owtli it may break into the retrobulbar space, or for- 
ward through the cornea and sclera ; it recurs after operation, and gives 
rise to metastases. 

A neuroglioma ganglionare (Fig. 275) is a tumor of the central 
nervous system, composed of hyperplastic gUa-tissue, ganglion -cells, and 



410 



TUMORS. 



nerve-fihres, and forms either poorly defined swellings of larger portions 
of the brain, or cirenmscribed, nodnlar enlargements of smaller jiortious. 
To the naked eye the stinietnre of the brain may in general appear to be 
still preserved, thongh the difference between the cortical and medullary 




Fig. 375.— Section from a nodular neuroglionui jraufflionare of the central con\ oliitiou of the cerebrum 
(Miiller's fluid, Weigert's stain). A, Portion of tissue rich in gansilion cells. Portion of tissue contain- 
ing nerve-fibres. C, jelly-like portion, a. Ganglion-cells arranged in groups ; /), scattered ganglion-cells ; 
c, ganglion-cells with two nuclei ; nerve-flbres with medullary sheath ; e, glia-cells ; /, blood-vessel. X 275. 



substance is less distinct than normal, and the tissue throughout is white 
or grayish -white, or spotted gray and white, and at the same time more 
or less hardened. 

The main portions of tliese masses consist of a more or less tliick glia- 
tissue containing a certain number of nerve-fibres (^) and ganglion-cells 
(rt, h, c), not only in the cortical region, but also in the white substance. 

Probably all of these formations are to be regarded as the result of 
disturbances of the embryonal development of the brain — tliat is, as 
local malformations of the brain, which have undergone further develop- 
ment during extrauterine life. 

As nenroepWielioma glioma tosum microcysticum there has been described by Rosen- 
thal a tumor extending over ten seonients of the spinal cord, wliich in its structure 
resembled a cystadenoma, and contained, in a gliomatous ground-tissue, gland-like 
formations and cysts lined with cylindrical cells of tfie character of ependy nia-epithelium. 

With reference to the origin of glia and ganglion cells from the ectoderm, various 
writers class the gliomaia in their different for infi witli the epithelial tumors. Against 
tliis view it may be urged tha-t the entire structure of these tumors favors their classifi- 
cation with the tumors dcrired from connective tissue and the supporting tissues. Glia- 
tissue is indeed a tissue which arises from a separation of ectodermal cells, but the 
middle germ-layer represents also a secondary formation from the inner germ-layer. 
In both tissues there occur such differentiations and transformations that the epi- 
thelial character is wholly lost. Even the ependymal epithelium, through its forma- 
tion of basal processes, approaclies in character the supporting cells. The especial 
position held by the nerve cells may be left out of consideration with a certain right, in 
so far as the classification of tumors is concerned, inasmuch as these cells only rarely 
and then only to a very limited extent occur as tumor-elements, or form lumor-like 
malformations. 



NEUROMA AND NEUROFIBROMA. 



411 



Literature. 

[Glioma and Neuroglioma.) 

Baumann: Zur Kenntniss der Gliome ii. Neurogliome. Beilr. v. Ziegler, ii,, 1888, p. 
500. 

Eisenlohr: Gliom der Netzbaut. Virch. Arch., 123 Bd., 1891. 

Emanuel: Gliom d. Pars cil. retinae. Vircli, Arch., 161 Bd., 1900. 

Ernst: Missbildung d. Kleinhirns. Beitr. von Ziegler, xvii., 1895. 

Gayet ct Poncet: Gliome de la retine. Arch, de phys., ii., 1875. 

Gerhardt: Glioma. Festschr. z. Sacularfeier der Universitat, Wurzbiirg, 1882. 

Greeff: Band. Glioma retinae. Deut. med. Woch., 1896. 

Heller: llirngliom. Tagebl. d. Naturforschervers. in Freiburg, 1883. 

Hoffmann: Gliom. Zeitschr. f. rat. Med., 34 Bd., 1869. 

Klebs: Hirngliom. Yierteljahrsschr. f. prakt. Heilk., 125 Bd. 

K'eumann: Gliom der Substantia perforata. Virch. Arch., 61 Bd., 1874. 

Petrina: Gliom. Prager Yierteljahrsschr., 133, 134 Bd. 

Pusey : The Genesis of Glioma Retin;e in Neuroglia. Johns Hopkins Hosp. Bull., 1902. 

Reising-er: Ueber das Gliom des Rlickenmarks. Virch. Arch,, 98 Bd., 1884. 

Rosentlial: Neuroepithelioma glioma tosum. Beitr. v. Ziegler. xxvii., 1900. 

Schuppel: Gliom u. Gliomyxom des Rlickenmarks. Arch, d. Heilk., viii., 1867. 

Simon: Spinnenzellen u. Pinselzellen im Gliom. Virch. Arch., 61 Bd., 1874. 

Steinhaus: Netzhautgliome. Cbl. f. allg. Path., xi., 1900. 

Stolpe: Eigenartiges Gliom. Festschr. d. Krankenh., Dresden, 1899. 

Stroebe: Bau u. Entstehung der Gliome. Beitr. v. Ziegler, xix., 1896. 

Thomas and Hamilton: Neuroglioma of the Brain. Journ. of Exp, Med., ii., 1897. 

Virchow: Die krankhaften Geschwulste, ii., 1864. 

Wintersteiner : Neuroepithelioma (Glioma) retinae, Wieu, 1896 (Lit.). 

{%) Neuroma and Neurofibroma. 

§ 112. The tumors designated neuromata occur most frequently on 
the ends of amputated nerves, where they form more or less prominent 
swellings, either circumscribed or blending into the surrounding tissne 
without any clearly defined demarcation. From the conditions of their 
origin they are known as ampuiation-iieuromata (Fig. 276, &). The devel- 
opment of these neuromata is to be referred to the changes taking place 
after the nerves have been severed ; during the development of connective 
tissue in the stump the ends of the axis-cylinders of the proximal portion 
of the affected nerve divide and grow longitudinally, so that the scar- 
tissue comes to be penetrated by nerves which at first have no sheaths, 
but are soon surrounded by medullary sheaths. The mass of nerves 
penetrating into the granulation tissue may be large or small, so that the 
connective tissue after a certain length of time may contain a very rich 
supply of nerves, which, radiating from the end of the old nerve, extend 
into the connective tissue in all directions (Fig. 276, h). The process 
is, therefore, an example of a useless regenerative proliferation of a nerve- 
stump exceeding the physiological needs. 

As another form of so-called neuromata are classed those growths 
. developing spontaneously, without external cause, along the course of 
nerves ; and which consist essentially of an increase in the connective tissue 
of the nerve, usually of the outer, more rarely of the inner layer of the 
endoneurium. 

At the point of tumor-growth the nerve-bundles become surrounded 
by a more or less thick layer of connective tissue, which is usually loose, 
more rarely dense (Fig. 277, h, d), or the bundles may be split apart 
into their individual fibres (c). Occasionally the perineurium takes 
part in the proliferation. In the case of large nerve-trunks the epineu- 
rium may be affected in association with the endoneurium and perineu- 



41^ 



TUMORS. 



rium of the individual bundles, although the process is most frequently 
confined to the endoneuriuni. 

According to their structure these tumors are not true neuromata, 
but are neurofibromata or fibromata of the nerves. They are usually 
of midtiple occurrence, and may extend throughout the entire iieripheral 
nervous system, but are more often limited to a definite area of nerve- 
distribution. In very rare cases they occur in the nerve-roots and spinal 
cord. The nodules are sometimes situated along the course of the 

nerve-trunks, sometimes on the finer 
branches, most frequently of the cutai e- 
' ' 7 ous nerves; and in the skin form more or 

less numerous, larger or smaller, timior- 
nodules, for the greater part of soft con- 
sistence, to which the designation muiti= 
I pie fibromata of the skin is usually 

applied. The smallest nodules can be 
seen only with the microscope ; the ma- 
^ jority vary in size from that of a pea to 

that of a hazel-nut. Individual tumors 
may reach the size of a man's fist, the 
■ nerve-fibres being wholly lost sight of in 
\ the great mass of connective tissue. At- 
\ rophy of the fibres may be caused by the 
y.; i; increasing connecti\e tissue, the fibres 

\\ finally vanishing completely. In addi- 

\ tiou to the formation of circumscribed 

nodules there may occur also in the af- 
teeted area a (///f'/^s^^ ////r/iY')?///^^ o///^^^ 7?("rm9 
^/ , ; fi-oin hypedropliy of their connective tlsme. 

/ ' Moreover, witli this condition there may 

I be associated a hypertrophic piolifera- 

\ tion of the connective tissue of the skin 

\ and sul^eutaneous tissue, leading to ele- 

l)Ji((nti((.si>i-(ike tJiicl'oiinr/s of the slin. 
|\ ? / A third form of false neuroma is the 

^ \ cirsoid neuroma (Bi uns) or plexiform 

neuroma (Yerneuil), a tnmor funnation 
which is characterized by the develop- 
^54, ^ ment in the domain of one or more nerve- 

^ branches of a convolution of tendril-like, 

Fi(.. M)iit itiMn-ueuroma of t-he fwistefl or luterwoveu thickened and 

sciiuic nerve ( Hint' Years after amputation LNNi^ttiU ui luiti \> u\ t;u, LUiL,ivt^ii«^u anu. 

of the nerve). LongitLRlinal section, a, nodular UervC-Strauds (Fio'. 278). A^TlCU 
Nerve: h. neuroma. Drawn from a . , . , , -i ,i • V • ^ 

preparation wMcli had been Irardened in examined in derail thlS tomiatlOll l.S alSO 

Muliers tiuid. X 3. fouud to depend e><sential]y upon a fibro- 

matosis of the nerves (Fig. 277), the pro- 
liferation of the endoneurimn resulting i^artly in a diffuse and partly 
in a nodular thickening of the nerves. In addition, it may be found 
In such formations that the nerves of the affected area are lengthened 
and thcreltii rendered tortuous, while at the same time the nerves are in- 
c)'r((.srd in iniinher, so that the number of tlie nerves of the skin and 
subcutaneous tissues is greater than under noi^mal conditions. The con- 
dition must, therefore, be regarded as one of true neuroma, a neuro)na 
verum associated witli fibromatosis. The nerves are for the greater part 
medullated {neuroma mijelinicum). It is very difficult to determine to 



NEUROMA AND NEUROFIBROMA. 413 

what extent uoii-niedullated iier\ es are 2:)reseiit in sncli formations, but 
nevertheless cases have been reported in which the nerve-fibres were for 
the greater part non-mediillated (neuroma amyelinicum). Cirsoid neu- 




TlG. :^T7.— Nerves from an elephantiasis-like cir'-. >iil nrur hki > f the cheek and lower jaw (Flemmin.^'s 
solution, safraniii I . (/. Nci ves, the outer layers of wh^^-e nul. >neiirlinu have luuler.iZ'one morbid pro- 
liferation; the nerve-tibres lie in the axial portion ; t\ ner\ e with markedly proliferated endoneuriuin aud 
separated nerve-libres : d. thickened nerve with a small strand of uerve-tlbres at the left end : c, loose con- 
nective tissue, rich in nuclei and containing fat, lying between the nerves. X 7. 



romata occur on the head, 
trunk, and extremities, and 
give rise usually to eJej)]u(iiti- 
asis-Jil'e distiguratio)is of the 
affected areas. 

True neuromata co7mst- 
ing of nerve-libres oin^. iKDinlinn- 
ceUs (^neuroma gn/if/I/ocrlh/hD-e 
verum) are rare tumors: but 
from the observations of 
Weichselbaum, Beneke. 
Busse, Kuauss, Schmidt and 
others, the occurrence of such 
growths cannot be doubted. 
They form tunu^rs varying in 
size from that of a millet-seed 
to tliat of an ax^ple, and de- 
velop particularly in the sym- 
pathetic system. In a case 
described by Knauss there 
were present multiple, nod- 
ular neuromata of the skin 
containing nerve-cells, and it 
is probable that these growths 
had their origin in sympa- 
thetic nerves containing gan- 




FiG. :i78.— rn-soid netu-oma of the sacral region. (After 
a drawnii;- bv P. P.i'uns). Ihe nodular, twisted, and inter- 
woven nerves are in part free ud, and in part (h) covered 
bv connective tissue. Natural size. 



414 



TUMORS. 



glion-cells. These tiimorvS consist of connective tissne, non-niedullated 
and medullated nerve-fibres, and ganglion-cells which resc^mblc those of 
the sympathetic ganglia. 

Both iho^ neurofibroma and the true neuroma are, as regards theii' origin, 
to be i^eferred to a congenital anlage. They form no metastases, bnt cases 
occni' in which neurofibromata take on a sarcomatons character and 
thereby become malignant. 

Literature. 

{Neuroma and Neurofibroma. ) 

Aschoff: Gescbwlilste. Ergebn. d. allg. Path., v., 1900. 

Beneke: Gangliose Neurome. Cbl. f. allg. Path., ix., 1898. 

Borst: Neuroma ganglionare. Sitzber. d. phys.-med. Ges., Wlirzburg, 1897. 

Bruns, P.: Ueber das Rankenneurom. Vn-ch. Arch., 50 Bd., 1870; Beitr. z. kliri. 

Chir., viii., 1891; Arch. f. kliu. Chir., 42 Bd., 1892. 
V. Biing-ner: Multiple Neurofibrome. Langenbeck's Arch., 55 Bd., 1897. 
Busse: Neuroma ganglioceliulare d. Sympathicus. Virch. Arch., 151 Bd., Suppl., 

1 S98. 

Courvoisier; Die Neurome, Basel, 1886, 
Czerny: Neurotibrom. Arch. f. klin. Chir., xvii., 1874. 
Esmarch u. Kulenkamp: Die elephantiastischen Formeu, Hamburg, 1885. 
Goldman: Beitr. z. Lehre von den Neuromen. Beitr. v. Bruns, x., 1892. 
Haenel: ISTeuroganglioma myelinicum. Arch, f. Psych., 81 Bd., 1898. 
Herczel: Ueber Fibrome u. Sarkome der peripheren Nerveu, Beitr. v. Ziegler, viii., 
1890. 

Jordan: Elephantiasis cougenita. Beitr. v. Ziegler, viii., 1890. 
Knauss: Echte multiple Neuronic. Vircli. Arch., 153 Bd., 1898, 
Krause: Ueber maligne Neuronic, 1887. 

Lecroix et Bonnaud: Nevronie plexiforme amyelinique. Arch, de med. exp., ii., 
18S0. 

Petren: Multiple allgem. Neuronic. Nordiskt Med. Ark., 1897. 

Preble and Hektoen: Multiple Fibromata of the Nerves, etc. Trs. Ass. of Amer. 
Piiys., 1900 (Lit.V 

V. Recklingliausen : Uc])er die multiplen Fibrome der Ilaut. Berlin, 1882. 
Schmidt: Ganglienzellenhalt. wahres Neurom d. Sympathicus. Virch, Arch, 155 
Bd., 1S99. 

Stienon: Etude sur la structure du nevrome, Bruxelles, 1883. 

Strube: C^ombinat. v. Neurotibrom niit Glioni. d. Kiickenmarks. Virch. Arch., 151 

lid., Suppl., 1898. 
Thomson: On Neuroma and Neurofibromatosis, Edinburgh, 1900. 
Verneuil et Depaul: Bull, de la soc. anat., Paris, 1857. 

Virchow: Die krankh. Gesclnviilste, iii. ; Das wahre Neurom. Virch Arch., 13 Bd., 
1858. 

Westphalen: Multiple Fibrome der Ilaut. u. der Nerven niit Uebergang in Sarkom, 

und ]\[etastasenbildung. Virch. Arch., 110 Bd., 1887. 
"Weichselbaum : Ganglioses Neurom der Nebenniere. Virch. Arch., 85 Bd., 1881. 

(A") Sarcoma. 

§ 113. A sarcoma is a connective -tissue tumor whose elements, either 
because of their number or often because of their size, predominate over the 
intercellular substance. Sarcomata are closely related to the undeveloped 
connective tissues, so that sarcomatous tissue may be compared with eyn- 
bryonal tissue. 

Sarcomata develop either in previously normal tissue belonging to 
the connective-tissue group — as, for example, in the skin, subcutaneous 
tissue, intermuscular connective tissue, periosteum, spinal cord, menin- 
ges, connective tissue of the glands, etc. — or in some preexisting con- 
nective-tissue tumor, as a fibroma, myoma, chondroma, hypertrophic 
lymphangioma, etc. , The transformation of the parent tissue into tumor 



SARCOMA. 



415 



tissue takes place through the growth and multiplication of the existing 
oells. The division of the cells takes place chiefly by mitosis, and mitoses 
are the more abundant the more rapid the growth of the tumor. In 
addition to typical mitoses there are frecxuently observed atypical forms, 
also nuclear fragmentation, and more rarely segmentation. 

In their fully develoi^ed state sarcomata form more or less sharply 
circumscribed growths. They may appear in a.nj portion of the body 
where connective tissue is present ; but are found in certain tissues more 
frecpiently than in others. Thus, for example, they are found much 
oftener in the skin, fascia, intermuscular connective tissue, bone-mar- 
I'ow, periosteum, brain, and ovaries, than in the liver, intestines, uterus, 
and lungs. 

The development and form of the cells vary greatly in different 
Siircomata. The intercellular substance is sometimes very scanty, soft, 
and delicate ; at other times more abundant and in character resembling 
the ground-substance of the mature normal connective-tissue substances. 

The amount of the intercellular substance has a marked intlueuce 
upon the consistence and color of the tumor. The medullary forms are 
soft and very cellular, and poor in intercellular substance; on section 
they present a marrow-like white or grayish-white surface. The hard, 
dense forms, on the other hand, are poor in cells and rich in fibrous inter- 
cellular substance; they pass by insensible gradations into fibromata. 
Transition-forms are known as fibrosarcomata. The cut surface of a 
sarcoma presents a nearly uniform appearance, in case retrograde changes 
or differences in the blood-content do not cause alterations of the same ; 
it is usually uniformly smooth, in the medullary forms milk-white, in 
the firmer varieties clear grayish-white, somewhat translucent, or more 
of a clear grayish-red or grayish-brown color. The hard forms are glis- 
tening white or yellowish -white. 

The development of the blood-vessels varies greatly ; sometiii'cs the 
vessels are very numerous, large, and ectatic (teJeangifcfatic sarcoma). 
Vsually the A essels have walls easily distinguishable from the tumor tis- 
sue; but the tumor-cells may also constitute the outer cells of the vessel- 
wall ; and in such a case the cells of the vessel-walls also take part in 
the growth of the tumor. Lymph vessels have not been demonstrated in 
sarcomata. 

Eetrograde changes — such as fatty degeneration, mucous degenera- 
tion, liquefaction, caseation, necrosis, haemorrhage, gangrene, ulceration, 
etc. — are of frequent occurrence in sarcomata. 

The sarcomatous tumoi\s may be divided into three classes. The first 
of these includes the simple sarcomata, or sarcomata in the narrower sense 
— that is, tumors of the tyj^e of embryonal connective tissue, showing a 
more or less uniform distribution of the cells without the formation of 
distinct groups of cells. The second class includes those sarcomata 
which show a special arrangement and grouping of the individual elements, so 
that tumor-formations arise which are very similar to the epithelial 
tumors. The third class is characterized by the appearance of secondary 
changes in the cells, in the intercellular substance, and inthe blood-vessels, these 
changes giving to the tumors concerned a characteristic appearance. 

The etiology of sarcoma not a simple one. It occurs more frequently 
in youth than in old age. Some sarcomata develop even in embryonic 
life, and the origin of such may be referred to some local malformation. 
Occasionally trauma appears to be an exciting cause. A i^arasitic origin 
has not been d(Mnonstrated (see Etiology of Carcinoma). Usually only 



416 



TUMORS. 



one primary tumor is formed, but multiple primaiy sarcomata sometimes 
occur, particularly in the skiu aucl bone-marrow. The softer tumors 
give rise to metastases. 

§ 114. The simple sarcomata include both soft medullary forms 
and those of a firmer consistence, which pass by insensible degrees of 
transition into the /7&rosarco»w(/a and _^?»'owi«f«. According to the char- 
acter of the cells, several forms may be distinguished. 

The small round=celled sarcomata are very soft, quickly growing 
tumors, which develop particularly in the connective tissue of the motor 
apparatus and supporting framework, and also in the skin, testicles, 
ovaries, and lymph-glands. On section they appear milky-white, and 
occasionally present caseous or softened areas. ^Yhen scraped the cut 
surface jaelds a milky fluid. Their structure is very simple ; the tumors 
consist almost wholly of round cells and blood-vessels (Fig. 279, c). 
The cells are small and frail; they possess very little protoplasm, and 
have spherical or slightly oval, rather large, bladder-shaped nuclei (r), 
which appear to be more highly developed than the nuclei of lympljoid 
cells. 

Between the cells lies a very scanty amount of fibrogranular intercel- 
lular substance. The vessels traverse the masses of cells in the form of 
thin-walled canals. If such a tumor growing in muscle be examined at 
its periphery it appears as an aggregation of round cells (Fig. 279, h, c) 
in the intermuscular connective tissue. Not infrequently lymphoid 
cells lie near the tumor-cells, the nuclei of the former (rZ) staining more 
intensely than those of the tumor- cells. 

A second form of round-cell sarcoma is designated lymphosarcoma 
or sarcoma lymphadenoides ; it imitates to a certain extent the struc- 




FUi. 279. Fk;. 280. 



Fig. 279. — Section tLirough the edsre of a sarcouia of the intermuscular connective tissue of the cervical 
muscles (alcohol, carmine), a, Transverse section of normal muscle : Oj. transverse section of an atrophic 
muscle-flbre; h, round cells cf the sarcoma, between the muscle-!ibi(^s ; c, fully developed tumor; d, leu- 
cocytes. X 300. 

FHi. 280.— Section from a lymphosarcoma of the nasal mucous membrane (alcohol, carmine), a. Retic- 
ulum; Z), cells of the reticulum; c. round cells: (i 'at tlie upper left), blood-vessel with proliferating^ 
cells. X 303. • 

ture of a lymph-gland in that the stroma for the greater part of tlie 
round cells consists of a vascular reticulum (Fig. 280, a), which in part 
at least is composed of branching and anastomosing cells (b), as may be 
demonstrated by shaking a small section of the tumor in a test-tube. 



SARCOMA. 



417 



According to the amount of the reticuliiin which they possess, the 
lymphosarcomafa may be di^ ided into the soft and hard form-s. In the 
denser varieties the leticiilar fi'amework may take on more and more 
the appearance of ordinarj^ fibrous connective tissue. 

Lymphosarcomafa arise most frequently in the lymph-glands and the 
adenoid tissue of the mucous membranes, in the spleen and medias- 




FlG. 281. FIG. 282. 



Fig. 281. — Section from a fungoid large round-celled sarcoma of the skin of the leg (carmine preparation). 

X 400. 

Fig. 282.— Section from a sarcoma of the mamma with cells of different shapes (alcohol, Bismarck- 
brown), o, Connective tissue ; h, sarcoma tissue ; c, small cells ; d, cells with hypertrophic nuclei; e, mul- 
tinuclear cells. X 300. 

tinum, but are found also in other places. The tumor-proliferation in- 
volves successively a more or less considerable portion of the lymph - 
adenoid tissues named. 

Large round=celIed sarcomata, the cells of which are much larger 
than those of the forms just described, appear in the same places as do 
the small round- celled variety, and closely resemble the latter. The cells 
possess an abundant protoplasm and large, bladder-like, oval nuclei (Fig. 
281). Many of the cells have two nuclei, some more than two. Between 
the round cells there lies a reticulated intercellular substance (Fig. 281), 
as well as spindle-shai)ed and branched cells, which together form an 
alveolar network in whose meshes lie the large round epithelial -like cells. 
Such tumors are designated large round-celled alveolar sarcomata (Billroth). 

In other forms of large round-celled sarcomata the tumor-cells are 
very unequal in size (Fig. 282), and at the same time there are mingled 
with the round cells elongated or irregularly shaped cells, so that the 
tumor may be called also a sarcoma with polymorphous cells. The 
nuclei likewise vary greatly in size (Fig. 282), and in individual cells (e) 
may be present in large numbers (niultinuclear giant-cells). 

The large round-celled sarcomata and the polymorphous- celled vari- 
ety are on the whole less malignant than the small -celled, but they also 
give rise to metastases. 

Spindle=cened sarcomata belong to the most commonly occurring 
tumors. As a rule, they are much firmer than the round- celled forms, 
but soft medullary forms also occur. On section they present ordinarily 
a grayish-white or yellowish-white, rather translucent surface, which 
may be more or less reddened according to its vascularity. Medullary 
tumors whose cells have undergone fatty degeneration may possess a 



418 



TUMORS. 



pure white color. In general, tliese sarcomata are more benign tlian the 
round -celled varieties, but their character in this respect varies according 
to their location and their richness in cells. 

According to the size of the cells there may be distinguished large 
spindled=celled and small spindle=celled sarcomata. Through the teas- 
ing of small pieces of the tumor the cells may in part be isolated, and in 
this way very long spindles may be obtained (Fig. 283). The cells lie 
side by side with their flat sides approximated, and are grouped in bun- 
dles, which, in sections, are cut partly longiiudinally, partly transvtMsely, 
and partly obliquely — e^ idence that they are interwoven in different 
directions. 

The arrangement of the spindles in bundles is often very striking ; 
in other cases it is wanting ; and the spindles for considerable distances 
run in the same direction. Sometimes the direction of the spindles is 
determined by the direction of tlie blood-vessels — that is, the individnal 
bundles form sheaths about their respective blood-vessels. 

Between the spindles there is often but a A^ery scanty intercellular 
substance, or it may not be possible to demonstrate in sections the pres- 
ence of such. In other cases it maybe more abundant, and show a fibril- 
lar character. The cells in such cases have less protoplasm, so that often 
it is scarcely possible to demonstrate any protoplasm aroujid the nucleus, 
and the processes at the poles of the cells seem to spring directly from 
the nucleus (nuclear fibres). Such varieties are dense and hard. They 




Fig. 283. Fig. :.'84. 

Fig. 283. - Spindle-cells from a large spindle-celled sarcoma of the cheek (.teased preparation). X 4(K1. 
Fig. 284.— Cells from a myelogenous giant-celled sarcoma of the tibia. (Haematoxylin.) x 400. 

cells are found also among the spindle-celled foi*ms; and contain spin- 
dle-shaped, pyramidal, prismatic, stellate, and verv irregular cell- forms 
(Fig. 284). 

Both in polymorphous- and spindle-celled sarcomata there may be 
found more or less numerous giant cells (Figs. 282, 284, and 285), so that 
the designation giant=celled sarcoma may be applied to these tumors. 



SARCOMA. 



119 



They arise particularly from the bones, but they may occur also in other 
places. 

If a sarcoma develops in preexisting new-growths there may be formed 
mixed tumors, which are known as myxosarcoma (Fig. 243), chondro= 



1 




Fig. 285. 



sarcoma (Fig. 248), myosarcoma, etc. The f<^i-niation of bone within 
a sarcoma leads to the formation of an osteosarcoma. 

The lymphosarcoma of the lymph-glands and lymphadenoid apparatus of the spileen 
and the mucous membrane of the gastrointestinal tract gives rise to a peculiar disease of 
these organs, Avhich is chai-acterized by a progressive increase of the lymphadenoid 
tissue, leading to the formation of extensive nodules. Under these circumstances the 
characteristic structure of the lymphadenoid apparatus is lost, and the newly-formed 
tissue shows a marked departure from the structure of typical lympliadenoid tissue — 
namely, a fibrous thickening of the reticulum or the formation of giant-cells. Since 
similar growths occur also in other organs, such as the liver, the disease cannot be 
looked upon as a pure hypertrophy of lymphadenoid tissue, but is closely related to 
tumor-formation. It is also possible that it is an infectious disease. Likewise the 
condition known as sarcomatosis cutis, which is characterized by the formation of nu- 
merous round-celled nodules in the skin, shows peculiarities which suggest an in- 
fection. 

Literature. 

(Sarcoma. ) 

Ackerman: Histogenese u. Histologic d. Sarkomc Sanunl. Id. Vortr., Nos. 233, 234. 
Leipzig, 1883. 

Beneke: Versprengung v. Nebennierenkeimen nebst Bemerkungen, etc. Beitr. v, 
Ziegler, ix., 189L 

Birch-Hirschfeld : Sarkom. Eulenburg's Realencyklop., xxi., 1899. 

Bizzozero: Stroma di sarcomi. Arch, per le Sc. Med., ii., 1878. 

Dreschfeld: Beitrag zur Lehre vom Lymphosarkom. Deut. med. Woch., 1891. 

Flexner: Multiple Lymphosarcomata. Johns Hopkins Hosp. Rep., iii., 1893. 

Goppert: Lymphosarkomatose. Virch. Arch., 144 Bd., Suppl., 1896 (Lit.). 

Goldmann: Verbreitungswege bosartiger Geschwiilste. Beitr. v. Bruns, xviii., 1897. 

van Heukelom: Sarcome et inflammation. Rec. de trav. du Lab. Boerhaave, 1899. 

Joseph: Hautsarkomatose. Arch. f. Derm., 46 Bd., 1898. 

V. Kahlden: Das Sarkom des Uterus. Beitr. v. Ziegler, xiv., 1893. 



420 



TUMORS. 



V. Karwowski: I'eber Callustiimoren. Inaug.-Diss., Freiburg-, lS9o. 
Lang-lians : Das nialigne Lympbosarkom. Vircli. Arch., 49 Jid., 1872. 
Lai'tigau: Primary Sarcoma of Tbyroid. Amer. Jourii. of Med. Sc., 1901 (Lit.). 
Linser: Sarkom der Haiit mit Scbrumpf iing. Beitr. v. Brims, 26 Bd., 1900. 
Lowentlial: Traumat. Entstebuug d. Gescbwiilste. Langenbeck's Arch., 49 Bd., 
is;,-). 

Manz: Riesenzellensarkom d. Brustdrlise. Beitr. v. Bruns, xiii., 1895. 
Neumann: Sarkome mit endothelialeii Zellen. Arcb. d. Heilk., xiii., 1892. 
Paltauf: Lympbosarkom. Ergebn. d. allg. Patb.. iii., 1897. 

Pawlowski: Parasitare Einscbllisse iu sarkomatosem Gewebe. Yircb. Arcb., 133 Bd., 
1893. 

Perl: Sarkom der Vena cava inferior. Yircb. Arch., 53 Bd., 1871. 
Putiata-Kerschbaumer : Das Sarkom des Aiiges, Wiesbaden. 1900. 
Sanger: Sarcoma uteri deciduo-cellulare. Arcb. f. Gyn., 64 Bd., 1893 (Lit,). 
Schmidt: Ueber das Angiosarkom der Mamma. Langenbeck's Arcb., xxxvi,, 1888. 
Sokolow: Ueber die Eutwickelung des Sarkoms in den Muskeln. Yircb, Arcb., 57 



Spieg-elberg-: Multipel auftretende Knockeusarkome. Inaug.-Diss., Freiburg, 1894. 

Steudener: Beitriige zur Onkologie. Yircb. Arcb., 59 Bd., 1874. 

Tillmanns: Beitr.'z. Lebre v. d. Sarkomen. Arcb. d. Heilk., xiv., 1873. 

Trambusti: Bau u. Tbeilung d. Sarkomzellen. Beitr. v. Ziegler, xxii., 1897. 

Virchow: Die kraukbaften Gescbwiilste, 2 Bd., 1864. 

Wieland: Primar multiple Knocliensarl^ome. Inaug.-Diss., Basel, 1893. 

Williams: Histologic u. Histogenese d. Uterussarkoms. Zeitscbr. f. Heilk., iv,, 

1894 (Lit.). 
See also §§ 115-117. 

§ 115. Sarcomata which present an organoid structure appear in 
those forms known as alveolar and tubular sarcomata. These are con- 
nective-tissne tnmors in which tlie cennhir elements, especiaUy the larger 
cells, are arranged in groups, so that it is possible to distinguish a vas- 
cular connective-tissue stroma and strands or nests of cells. According to 
their genesis, these growths may be divided into two types : lymjyJiangiosar- 
conia and Immangiosarcoma. There are, however, also alveolar sarcomata 
which possess stroma and cell-nests, but which, in so far as their devel- 
opment is concerned, cannot be included with the above-named types. 

The lymphangiosarcomata are tumors which arise from a j>ro?//(sra- 
tion of the endothelium of the lymph-vessels and lymph-spaces. They may 
accordingly be designated as lymphangioendotheliomata or as endo- 



normal tissue, or in preexisting tmnor-like formations, such as the hy- 
pertrophic lymphangioma in particular (pigmented moles and warts, 
see § 109), aud also from myxochondromata. The first occur particularly 
in the meninges of the brain, and in the serous membranes of the great 
body- cavities ; but may develop also in other organs; the second are 
found chiefly in the skin ; while those arising from myxochondromata 
develop in the mixed tumors of the salivary glands, palate, and orbit. 

The endotheliomata of the inner meninges of the brain and spinal cord 
occur partly as nodular growths and partly as flattened proliferations; 
they develop through the transformation of the flattened endothelium, 
which covers the connective-tissue network of the subarachnoideal tissue 
and pia, into cubical or even cylindrical cells (Fig. 286, d, e). In con- 
sequence, the new-growth at first presents the appearance of gland-like 
formations ; in the event of a more active proliferation solid nests of cells 
are formed. Inasmuch as the pia is continued as a lymph-sheath around 
the cerebral vessels, there are formed around the latter strands of large 
epithelial-like cells (Fig. 286,/, g, h). 

The endothelioma of the dura mater arises through a proliferation of the 
endothelium of the lymph -vessels, and leads, through the filling up of 



Bd.. 1873. 



theliomata in the narrower sense. 




SARCOMA. 



421 



the latter with large cells, to the formation of auastomosiiig cords of cells 
(Fig. 287, c, d, e), which in some i^laces maj^ still contain a Inmen. 

The endotheUomata of the pleura or of tJie peritoneum appear usually as 
flattened thickenings of the affected membrane, but scattered nodular 
elevations may occur throughout the areas of thickening. These growths 




0 



Fig. 286.— Section through an endothelioma of the pia mater and cerebral cortex, diffusely spread over 
the surface of the brain and spinal cord (Miiller's fluid, h£eraatoxylin). a, Superficial pia; h, pia in a 
sulcus; c, cortex; d, e, endothelial proliferations in the pia sheaths of the cortical vessels ; /, (/, endo- 
thelial proliferations in the pia sheaths of the cortical ves.sels ; t, lono'itudinal section through a vein. X 38, 

are characterized by cords of large cells (Fig. 288, which, corresi)ond- 
ing to the course of the lymph- vessels, traverse the hypertrophic and 
proliferating tissue of the serosa. 

The endothelioma of the mammary gland is a rare tumor, which develops 
in the form of nodules, and takes its origin from a proliferation of the 
endothelium of the lymph-vessels and lymph-spaces (Fig. 289, h, c), and 
gives rise to the formation of large cords of cells (c) or of smaller cell- 
nests. The proliferating cells are characterized by a great variation in 
the size, character, and form of the nucleus and cell-body. 

The endothelioma of the sMn, which arises from the hypertrophic lym- 
phangioma (warts and pigmented moles), resembles these in its general 
structure, and possesses also cell- nests of varying size (Fig. 268). Fur- 
ther, there also occur endotheliomata of the skin, which do not arise from 
warts, and may develop in great numbers (Spiegler, Mulert). 

The eiidothelial proliferations lohich arise in myxomata and m,yxochondro- 
mata form cords of cells of different shapes (Fig. 243, b) ; but it should 
be noted that in these cases similar proliferations may also arise from the 



422 



TUMORS. 



blood-vessels (Fig, 293, c, d), so that it is often impossible to decide as 
to the nature of the cell -strands. 

The alveolar, tubular, or plexiform structure of the endothelioma is 
well marked only in the first stages of the tumor, and usually disappears 





r 

Fig. 287.— Endothelioma durae matris (Miiller's fluid, haematoxylin). a. Connective-tissue stroma; h- 
small-celled focus ; c, groups and strands of cells arising? from the proliferation of lymph-vessel endothe- 
lium ; d, endothelial cell-strand vv^ith a lumen ; e, area of fatty degeneration in nest of endothelial cells ; 
strand of cells, passing gradually, on the right, into the surrounding connective tissue. X 5^5. 

in part with the advancing growth of the tumor. This is due, on the 
one hand, to the fact that the endothelial proliferation extends, without 




■Mm 




Fig. 288.— Endotheliou 



of the pleura (alcohol, haematoxylin). a, Proliferated and thickened pleural con- 
nective tissue : b, cell-strands. X 100. 



sharp limits, into the neighboring connective tissue (Fig. 287, /) ; and, 
on the other hand, to the circumstance that the connective-tissue cells 



ENDOTHELIOMA. 



423 



take on a proliferative activity similar to that of the eudothelium, so 
that there is formed a diffuse, cellular new growth of the character of 




Fig. 289.— Endothelioma of the mammary gland (alcohol, htematoxylin. eosin). a. Connective tissue; Z), 
enlarged cells in the connective-tissue spaces ; c, strands of cells ; (/, diffuse cell-proliferation. X 300. 

an ordinary sarcoma (Fig. 289, d). Accordingly, the endotheliomata 
cannot be sharply distinguished from the sarcomata, and may become 
transformed into the latter. 

The similarity in structure between endotlieliomata and carciuomata raises tlie 
question whether it would not be expedient to class the former as emlothelinl cancers. 
The structure of these tumors would certainly justify such a classitication, but I con- 
sider it better to avoid the use of this term. In the first place, the term endothelioma 
is in general use and is entirely appropriate, and the introduction of the term endothe- 
lial cancer would easily give rise to confusion; by the term cancer in general is under- 
stood an epithelial tumor, and it does not seem expedient to introduce two types of 
cancer — an epithelial and an endothelial. 

I have classed as endotheliomata those tinnors of the serous membranes which are 
characterized by the formation of cell-cords in the lymph channels, on the assumption 
that these cords of cells arise from the endothelium of the lymph-vessels and lymph- 
spaces. I must admit, however, that I do not consider this assumption as absolutely 
proved, in spite of the concurring definite statements of a number of authors (see 
Glockner). The possibilit}^ of their development from the epithelium of the serosa is 
not excluded (Bencla), and if such an origin could be proved, the question would arise 
whether it would not be better to class these tumors with the carcinomata, since the 
corresponding tumors of the kidneys and ovaries, whose gland-cells arise from peri- 
toneal epithelium, are classed with the epithelial tumors. 



Literature. 

{ Endoth elioma [Lympliangiosarcomct] . ) 

Adler: Primary Endothelioma of the Pleura. Jour, of Med. Ees., 1901. 
Earth.: I.ymphangiosarkom d. Mundbodens. Beitr. v. Ziegler, xix., 1896 (Lit.). 
Benda: Primares Carcinom d. Pleura. Dent. med. Woch.,"l897. 
Bohme: Primares Sarko-carcinom der Pleura. Virch. Arch., 81 Bd., 1880. 
Driessen: Unters. lib. glykogenreiche Endotheliome. Beitr. v. Ziegler, xiii., 1892, 
Eberth u. Spude: Familiare Endotheliome. Yirch. Arch., 153 Bd., 1898. 
Pranke: Endothelioma intravasculare hyalogenes Virch. Arch., 121 Bd., 1890, 



424 



TUMORS. 



Gebhardt: Endotlieliom der Pleura, Inaug. -Diss., Freiburg, ]894. 

Glockner; Endotlielkrebs d. serosen Hilute. Zeitscbr, f. lleilk., xviii., 1897 (Lit ); 
Riesenzellen u. endothelialc Gescbwiilste. Beitr. v. Ziegler, xxvi., 1899. 

Kelly: Tlie Histology and Histogenesis of Certain Tumors of tbe Parotid, with Par- 
ticular Peference to Those of Endothelial Origin. Phila. Month. Med. Journ., 
1899. 

Kromayer: Endothelioma tuberosum colloides. Yirch. Arch., 139 Bd., 1895. 
Krompecher: Endotlieliom des Hodens. Yirch. Arch., 151 Bd., Suppl., 1898. 
Kiittner; Geschwulste der Submaxill aris. Beitr. v. Bruns, xvi., 1896 (Lit.). 
Lancereaux; Traite d 'anatomic pathol., iii., Paris, 1889. 

Linser: Yerkalkte Epitheliome und Endotlieliome. Beitr, v. Bruns, xxvi., 1900. 
Marchand ; Eudotheliom d. Antrum Highmori mit hj'al. Kugeln. Beitr. y. Ziegler. 
xiii., 1893. 

Markwald: Multiples intra vasculitres Endotheliom d. Knocben. Yirch. Arch., 1-41 
Bd., 1895. 

Mulert: Multiple Endotheliome der Kopfhaut, Langenbeck's Arch., 54 Bd., 1897. 
Neumann, E, : L^eber Sarkome mit endothelialen Zelleu. Arch, d, Heilk., xiii., 1872. 
V. OMen: Beitr. z. Kenntn. d. Parotisgeschwiilste. Beitr. v. Ziegler, xiii., 1893. 
Perls: Beitr. z. Geschwulstlehrc. Yirch. Arch., 56 Bd., 1872. 
Perthes: Yerkalkte Endotheliome, Beitr. v. Bruns, xii., 1894. 

Pollmann: Endotheliom d. Pleura u. d. Peritoneums. Beitr. v. Ziegler, xxvi., 1899. 
Rindfleisch. u. Harris: Endotheliom des Knochenmarke^. Yirch. Arch., 103 Bd.^ 
1886. 

Hitter: Fettgehalt der Endolheliome d. Knochen. Zeitschr. f. Chir., 50 Bd., 1899. 
Rossier: Cancer primitif de la plevre. Beitr. v. Ziegler, xiii., 1893. 
Schulz, R. : Das Endothelcarcinom. xVrcli. d. Heilk., xvii., 1876, 
Tanaka: Endotheliome (bes. d. Haut). Deut. Zeitschr, f. Chir., 51 Bd., 1899. 
Teixeira: Zur Casuistik des primaren Pleuraendothelioms. Inaug. -Diss., Freiburc;, 
1894. 

Volkmann: Endothelialc Geschwulste. Deut. Zeitschr. f. Chir., 41 Bd., 1895 (Lit.). 
Waelsch: Aus weichen Naevi entsteh. bosart. Ge.schw. Arch. f. Derm., 49 Bd., 1899. 
Warthin; Endothelioma of the Lachrymal Gland, Arch, of Ophth., 1901. 
See also g§ 114 and 116. 

§ 116. The h^emangiosarcomata represent a group of organoid sar- 
comata, in which the walls of the blood-vessels and their surrounding 




Fig, 290,— Blood-vessel endothelioma of the kidney (formalin, haematoxylin, eosin). a. Vessels filled 
with blood ; h, vessels filled with proliferated endothelial cells. X 300. 



ENDOTHELIOMA. 



425 



tissue take an especial part in the bnildiug-np of the tumors, and con- 
stitute a characteristic feature of their structure. 

One form of haemangiosarcoma is the bIood=vessel=endotheIioma or 
hasmangioendothelioma, a tumor which arises, either from preexisting 




Fig. 291.— Section through a nodular angiosarcoma of the thyroid (Flemming's solution, safranin). a 
Transversely cut vessels ; h, perivascular cylinders of cells cut transversely and showing numerous mitoses ; 
c, granular masses, with scattered cells, between the cell-cylinders. X 73. 



blood-vessels or those newly formed in htemangiomata, through a more 
active develop Jient and proliferation cf the endothelium giving rise to 




Fig. 292.— Angiosarcoma of the testis (Miiller's fluid, hrematoxylin, eosinK a. Perivascular masses of 
closely packed cells ; 7>, areas poor in cells ; c, hyaline lumps ; d, hyaline masses containing blood ; e, semi- 
niferous tubules ; /, large vein, x 80. 



4:26 



TUMORS. 



blood-vessel spaces lined Tvith cubical or cylindrical endothelium (Fig. 
290), or to canals coin]3letely filled with such cells (b). According to 
the number of blood-containing vessels the tumor is either dark-red, 
pale, grayish-white or yellowish-white. The endothelial cells, according 
to the stage of development, may contain glycogen or fat or both. 

A second form of hsemangiosarcoma, the haemangiosarcoma in a 
narrow sense (occasionally also called perithelioma), arises through the 
X^roliferation of the tissue of the outer layers of the blood-vessel walls 
and their immediate surroundings, so that the vessel -lumina are sur- 
rounded by a more or less thick mantle of cells (Fig. 291, h). 

In typical cases the tumor- tissue consists almost wholly of a confused 
tangle of blood-vessels (Fig. 291, a), whose walls are surrounded by a 
thick layer of cells, which often reach to the endothelium. The thick- 
walled tubes of cells sometimes run an isolated course, and at other times 
anastomose, so that variously formed twistings and interweavings result 




Fig. 298.— Chondrofibroma of the parotid with angiosarcoma (Miiller's fluid, hiPiuatoxylin. eosin). a. 
Areas of oartila.s'e ; 7), dense sarcoma tissue ; c, blood-vessel ; d, cell-strands arising from blood-vessels, and 
in part containing a hyaline substance. X 80. 



{plexifonn angiosarcoma). The tissue lying between the cell-strands is 
tlie remains of the original tissue (Fig. 292, h), and may still contain 
characteristic tissue-formations, as, for example, glands (^e). 

Should a more active iDroliferation of the perivascular mantle of cells 
occur, and if these become confluent with each other (Fig. 292), the tumor 
passes over into an ordinary sarcoma. This change almost invariably 
occurs in the larger tumors of this kind. 

Hsemangiosarcomata occur in the most varied organs : testicles, kid- 
neys, salivary glands, bones, brain, mamma, thyroid, skin, carotid gland, 
ovaries, and liver. In the last-named organs they are rare. Both forms 



ENDOTHELIOMA. 



427 



may so occur that the tumor throughout bears the character of a haeman- 
giosarcoma ; but it also happeus that such proliferations of the vessels 
form only a single feature of other 
tumors (Figs. 293, c, d; 300, d)-, 
and though this feature indeed 
gives character to indiv idual por- 
tions, it is, on the whole, over- 
shadowed by other features of the 
growth — as, for example, a fibro- 
cellular tissue, cartilage (Fig. 
293, a, 1)), or myxomatous tissue 
(Fig. 300, a). 

Lyniphangiosarcomata and 
hsemangiosarcomata cannot al- 
ways be sharply differentiated 
from each other, and tumors 
occur to which both designations 
may be applied with propriety. 
The perivascular development of 
the endothelial proliferation with- 
in the brain in endothelioma of 
the pia (Fig. 286, /, g, h) would 
justify also the application of the 
term hsemangiosarcoma. 

If in a lymj)hangiosarcoma of 
the skin there is such a rapid de- 
velopment of the cell -nests that the space between the vessels becomes 
wholly filled with cells, so that the framework of the tumor comes to 
consist onl}^ of blood-vessels (Fig. 294), it becomes an open question as 
to whether the tumor should be called a lymphangioendothelioma or a 
hsemangiosarcoma. 

Literature. 

(Scemangioscucoma \_EndotlieJloma]. ) 

Arnold: Piimare Angiosarkome der Leber. Beitr. v. Ziegler, viii., 1890. 
Borrmann; Blutgefassendotlieliom. Vircli. Arch., 151 Bd., 1898; Wachstlmm d. 

Gefassgeschwulste. lb., 157 Bd., 1899. 
Harris: Malignant Disease of tlie Pleura. Journ. of Path., ii., 1893. 
V. Heinleth: Perithelioma gland, caroticae. Cbl. f. allg. Path., xi., 1900. 
Hildebrand: Tnbulares Angiosarkom der Knochen. Deut. Zeitschr. f. Chir., 31 Bd., 

1890; Nierentumoren. Arch. f. klin. Chir., 47 Bd., 1894. 
V. Hippel: Ziir Casuistik der Angiosarkome. Beitr. v. Ziegler, xiv., 1893. 
Jarisch.: Hautgeschwiilste (Hamangioendotheliom). Arch. f. Derm., 28 Bd., 1894. 
Jolly: Angiome sarcomateux. Arch, de med. exp., vii., 1895. 
Kolaczek: Ueber das Angiosarkom. Deut. Zeitschr. 1 Chir.. ix. and xiii. 
liimachet: Blutgefassendotheliom. Virch. Arch., 151 Bd., SuppL, 1898. 
Low and Lund: Tubular Perivascular Sarcoma. Journ. of Med. Res., 1902. 
Marchand: Anat. d. Glandula carotica. Intern. Beitr., Festschr. f. Yirchow, ii., 

1891. 

Maurer: Beitr. z. Kenntniss des Angiosarkoms. Yirch. Arch., 77 Bd., 1879. 
Neumann: Ueber Sarkome mit endothelialen Zellen. Arch. d. Heilk., xiii., 1872. 
Paltauf: Geschwlilste der Glandula carotica (Angiosarkom). Beitr. v. Ziegler, xi.. 
1892. 

de Paoli: Primares Angiosarkom der Niere. Beitr. v. Ziegler, x., 1891. 
Putiata: Ueber Sarkome der Lymphdrtisen. Yirch. Arch., 69 Bd., 1877. 
Ritter: Fetthaltiges Endotheliom der Knochen. Zeitschr. f. Chir., 50 Bd., 1899. 
Sailer: Primary Endothelioma of Left Sup. Pulm. Yein. Cont. from the Willian 
Pepper Labor., 1900. 




Fig. 294.— Alveolar melanotic sarcoma of the skin 
(alcohol, hfematoxylin). a. Mononuclear, a,, multi- 
nuclear sarcoma cells of epithelial character; I), pig- 
ment-containing cells; c, stroma with blood-vessels 
and pigment. X 300. 



428 



TUMORS. 



Scliniidt: Ueber das Angiosarkom der Mamma. Arcli. f. klin. Cliir., 36 Bd., 1887. 
Waldeyer; Die Entwickelung der Carcinome. Yirch. Arch., of) Bd., 1872. 
Wolters: Haemangioendotlielioma tuberos. inultipk'X cutis. Arcli, f. Derm., 58 Bd., 
1900. 

See also 115 and 117. 



§ 117. Sarcomata which acquire a peculiar character through 
especial products of the cells or through changes in their ground= 
substance are to be found both among the simple and the organoid forms. 
The chief types belonging in this class are the melanosarcoma, chloroma, 
osteoid sarcoma, the petrifying sarcoma, psammoma, and the sarcomata 
containing hyaline formations. 

Melanosarcomata occur in tissues which contain pigmented connec- 
tive-tissue cells — cliromatophores. They develop most frequently in the 
choroid of the eye and in the skin. In the latter case they arise chiefly 
from pigmented moles and lentigines. They belong to the malignant 
sarcomata, grow into the neighboring tissues, and give rise to metastases. 
The fully developed tumor is in whole or in part smoky gray to black or 
brownish-black, the color being due to the j^resence of round, angular, 
fusiform, and branched cells, which are filled with j^ellowish-brown pig- 
ment granules (Figs. 294, h, e; 295, c"), or are stained a diffuse yellow. 
In the alv^eolar forms both the large cell -nests, as well as the smaller cells 




Fig. 295.— Melanotic sarcoma of the skin (alcohol, carmine, eosin). a, S^arcoma tissue rich in cells ; b, cell- 
nests ; c, pigment-cells ; d, blood-vessels with hyaline walls. X SOU. 



of the supporting framework, may contain pigment. It is often especially 
abundant in the neighborhood of the blood-vessels (Figs. 294, e; 295, 
d) ; but this pigment is not hsemosiderin (see § 70). 

The metastases are likewise more or less pigmented (Fig. 296) ; and 
the smallest ones may consist essentially of pigmented cells (c, d). Oases 
occur in which numerous organs, the skin, muscles, pia, serous mem- 



CHLOROMA. 



429 



branes, and adipose tissue (Fig-. 296) are spotted black through the for- 
mation of innumerable metastases. 

Chloromata are tumors the cut surface of which presents a light- 
greeu color which on exposure to the air takes on a dirty appearance. 




Fig. 296.— Metastasis of a melanotic sarcoma of the skin in the mesentery of the small intestine (forma- 
lin, aliim-carminej. a, Peritoneum ; b, fat tissue ; c, sarcoma nodule ; d, isolated chromatophores. X 280, 



They develop most frequently from the periosteum of the cranium; 
and consist of tissue made up of round cells and a reticular stroma. 
They may, therefore, be classed with the lymphosarcomata. 

According to Chiari and Gruber, the green color is due to the pres- 




9^ 



9 



Fig. 297.— Osteoid sarcoma of the ethmoid hone (Miiller's fluid, hasmatoxylin, eosin), rt. Sarcoma tissue ; 
b, osteoid tissue ; c, old bone-trabeculse ; d, vascular fibrous tissue. X 45. 



430 



TUMORS. 



ence in the cells of small sliiniiig spherules which give the microchemical 
reactions of fat. In harmony with this view is the fact that the color 




Fig. 298.— Petrifying large-celled sarcoma of the tibia (Miiller's fluid, haeinatoxylin, eosin), a. Poly- 
morphous tumor-cells ; b, alveolar stroma ; c, trabeculee of stroma containing small calcareous concre- 
tions ; d, petrifying trabeculae of the stroma. X 



disappears in alcohol. On the other hand, von Eecklinghausen holds 
that the color is a property of the parenchyma. 

Osteoid sarcomata develop in the bone-marrow and periostemn, and 
are characterized by a thickening of the gronnd-snbstance in certain 
areas, so that there are formed traheculce of osteoid tissue (Fig. 297, b). 
Snch tnmors are closely related to the osteosarcomata but differ from 
them in the absence of deposits of lime-salts. 

Petrifying sarcomata likewise occur most frequently in connection 
with the skeleton, and are characterized by the development between the 

tumor- cells of trabeculae of a deli- 
cate ground-substance (Fig. 298, 
c),. through the calcification (d) of 
which the tumor tissue becomes 
hardened, although no typical 
bone is formed. 

Psammomata or sand tumors^ 
(acervulomata) are sarcomata or 
fibrosarcomata of the dura, in- 
ner meninges, or pineal gland, 
which contain concretions of lime- 
salts in greater or less abundance. 
Some of these concretions are sim- 
ilar in structure to the normal 
brain-sand, the basis of their for- 
mation being concentric layers of 
cells which have undergone hya- 
line degeneration (Fig. 299, a, 
b, c). Occasionally the chalky 
spherules lie inside of individual 
cells and represent hyaline products of the cells which have later become 
calcified. Others are more of the nature of spicules ' ((^), and arise 
through the deposit of lime-salts in connective tissue or blood-vessels 
which have undergone hyaline degeneration. 




Fig. 299.— Section from a psammoma of the dura 
mater (alcohol, picric acid, hasmatoxylin, eosin). a. 
Hyaline nucleated spherule inclosing calcareous con- 
cretion; Ik calcareous concretion with hyaline non- 
nucleated border, inclosed in fibrous connective tis- 
sue ; c, calcareous concretion surrounded by hyaline 
connective tissue; (7, spicule of lime in the connec- 
tive tissue ; e, spicule with three concretions, x 180. 



SARCOMATA WITH HYALINE FORMATIONS. 



431 



Psammomata usually form round nodules, and may be of multiple 
occurrence. 

Sarcomata with hyaline formations (the myxosarcomata excepted) 
arise as follows: Either the cells form hyaline products^ or they themselves 
become converted into such, or the fully developed connective tissue and the 
blood-vessels undergo hyaline degeneration. These changes may take place 
in simple sarcomata as well as in endotheliomata and hsemangiosarcomata ; 
but occur much more frequently in the last-named tumor-forms (Figs. 
288, b ; 293, d; 300). The hyaline masses may form spherules, or club- 
like forms, or cords, or net-like or cactus-like figures. They push the 
cells apart, and often reduce them to narrow strands. Billroth has des- 




FiG. 300.— Myxo-angiosarcoma of the parotid, with hyaline formations (Miiller's fluid, htematoxylia, 
fosin). fl, Myxomatous tissue; h, cell-strands Inclosinpf hyaline spherules ; c, hyaline spherules in myxo- 
matous tissue ; d, blood-vessels with proliferatincf endothelium and hyaline spherules. X 90. 

igliated such tumors as cylindromata. In en.dotheliomata the hyaline de- 
generation may be associated with the formation of laminated masses of 
fattened cells like the layers of an onion, around a nucleus. 

Hyaline degeneratioyi of the vessel-walls and of the connective -tissue bundles 
results in a thickening of the same (Fig. 295, d), sometimes uniformly 
and sometimes irregularly distributed. Hyaline products of cells have a 
tendency to assume a spherical form (Figs. 288, b; 293, d; 300, c, d). 
The disintegration of larger cell-masses with hyaline change leads to the 
extensive formation of hyaline spherules, strands, or branching struc- 
tures. 

If, in endotheliomata and angiosarcomata, the cord-like masses of 
cells which have been formed within the lymph- or blood-vessels become 
converted into hyaline masses, there will be produced formations which 
greatly resemble glands containing colloid (Fig. 300, d) : and which 
have often been mistaken for such. 



432 



TUMORS. 



Eibhert regards the melanosarcoma as an especial form of tumor arising from the 
chromatophores, and would for this reason separate it from the sarcomata as an individ- 
ual tumor-type. It is to be noted, however, that in the development of the melanotic 
sarcoma other cells besides the chromatophores take on proliferative activity ; so that 
melanotic sarcomata can be regarded only as sarcomata in whose development certain 
cells, which possess the power to form pigment, have taken part. 

Literature. 

(Melanotic Sarcoma. ) 

Achenbacli: Orbitales Melanosarkom. Yircli. Arch., 143 Bd., 1896. 
Dietrich; Beitr. z. Statistik u. klin. Bed. melanot. Geschwlilste. Arch. f. kliu. Chir., 
XXV., 1867. 

Dobbertiri Melanosarkom d. Kleinhirns. Beitr. v. Ziegler, xxviii., 1900. 
Eberth: Ueoer die embolische Verbreitung der Melanosarkome. Virch. Arch., 58 Bd., 
1878. 

Gonin: Sarcome pigmente de la cornee. Beitr. v. Ziegler, xxiv., 1898. 
Hirschberg u. Birnbacher: Sarcoma melau. corp. cil. et chorioideae. Cbl. f. 
Augenlieilk., 1884. 

Just: Ueb. d. Verbreit. d. melanot. Geschw. im Lvmphgefasssvstem. Inaug.-Diss., 
Strassburg, 1888. 

Kolaczek: Zur Lelire von der Melanose der Gescliwiilste. Deut. Zeitschr. f. Chir., 
xii. 

Leber : Aderliautsarkome. Arch. f. Ophthalm., 44 Bd., 1897. 

Martens: Eutwickelung d. Melanosarkoms d. Chorioidea. Virch. Arch., 138 Bd., 
1894. 

Maurer: Beitr. z. Kenntniss der Angiosarkome. Virch. Arch., 77 Bd., 1879. 
Morner: Zur Kenntu. d. Farbstoffes in melan. Geschw. Zeitschr. f. phvs. Chem., 11 
Bd., 1887. 

Oppenheimer : Pigmentbildung in melanot. Geschwlilsten. Virch. Arch., 106 Bd., 
18S6. 

Putiata-Kerscbbaumer : Das Sarkom des Auges, Weisbaden, 1900. 
Ribbert: Das ]\Ielanosarkom. Beitr. v. Ziegler, xxi., 1897. 

Schalek: Contribution to the Histogenesis of Melanotic Sarcoma of the Skin. .Tourn. 

of Cutan. and Gcnito-urinary Diseases, 1900. 
Steinmetz: Ein Fall von Melanosarkom mit ausgedelmter Metastase. Inaug.-Diss., 

Freiburg, 1891. 
Virehow: Die krankhaften Geschwlilste, ii., 1864. 
"Wag-ner: 19 Falle von Melanosarkom. Munch, med. AVoch., 1887. 
"Wallach.: Beitr. z. Lehre vom Melanosarkom. Virch. Arch., 119 Bd., 1890. 
Wiener: Melanosarkom d. Bectums. Beitr. v. Ziegler, xxv., 1899. 
Williams: Melanotisches Uterussarkom. Zeitschr. f. Heilk., xv., 1894. 

{ChJoroma.) 

Cbiari: Chlorom. Zietschr. f. Heilk., iv., Prag, 1883. 

Dock: Chloroma and its Relation to Leuksemia. The American Journ. of the Med. 
Sc., 1893. 

Dressier: Ein Fall v. sogenanntem Chlorom. Virch. Arch., 85 Bd., 1866. 
Horing": Zur Kenntn. d. Chloroms. Arb. lier. v. Baumgarten, 1., Braunschweig, 
1891. 

Huber: Ueb. d. sog. Chlorom. Arch, d Heilk., xix , 1878. 

V. Recklinghausen : Tagebl. d. 58 IS'atui-f orschervers. in Strassburg, 1885. 

Virehow: Die krankh. Geschwlilste, ii., 1864. 

Waldstein: Chlorolymphom. Virch. Arch., 91 Bd., 1883. 

(Fsammoma.) 

Arnold: Zur Lehre v. d. Bau u. d. Eutwickelung d. Psammome. Virch. Arch., 52 
Bd., 1871. 

Ernst: Ueber Psammome. Beitr. v. Ziegler, xi., 1892. 

Golg-i: Bau u. Eutwickelung des Psammoms. Virch. Arch., 51 Bd., 1870. 

Levi: Untersuch. liber d. Bau u. d. Entstehung d. Concretionen in Psammomen der 

Dura mater cerebri u. d. Kalkplattchen der Arachuoidea spinalis. Inaug.-Diss., 

Freiburg, 1891. 



THE EPITHELIAL TUMORS. 



433 



liinser: Verkalkte Endotlieliome. Beitr. v Brims, xxvi., 1900. 

Petroni: Sarcome angiolithique. La Roumaine med., 1893. 

Steudener: Zur Kenntniss der Sandgeschwulste. Virch. Arch., 51 Bd., 1870, 

Virchow: Die krankhaften Geschwiilste, ii., 1864. 

(Sarcoma with Hyaline Formations.) 

Billroth: Untersuchungen liber die Entwickelung der Blutgefasse, 1856. 
Dag-onet: Cylindrome de la dure-mere. Arch, de med. exp., iv., 1892. 
V. Dembowsky : Cylindrom der Nase. Zeitsclir. f. Cliir., 32 Bd., 1891. 
Ewetsky: Zur Cylindromfrage. Virch. Arch., 69 Bd., 1877. 
Franke: Beitr. zur Geschwulstlehre. Virch. Arch., 121 Bd., 1890. 
Friedlander : Gescliwulste mit hyaliner Degeneration. Virch. Arch., 67 Bd., 1876. 
Koester: Kankroid mit hyaliner Denegeration. Virch. Arch., 40 Bd., 1867. 
Lubarsch.: Krebs des Ileums. Virch. Arch,, 111 Bd. ; Cylindrome. lb., 122 Bd., 
1890. 

Maier: Beitrag zur Cylindromfrage. Virch. Arch., 14 Bd., 1858. 
Malassez: Sur les cylindromes. Arch, de phys., 1883. 

Marehand: Endotheliom d. Antrum Highmori mit hyalinen Kuireln. Beitr, v. 
Ziegler, xiii., 1893. 

Pagenstecher : Beitrag zur Geschwulstlehre. Virch. Arch,, 45 Bd., 1869. 
Sattler: Ueber die sog. Cylindrome, Berlin, 1874. 
See also §§ 115 and 116. 

2. The Epithelial Tumors. 

(a) General BemarJcs. 

§ 118. The epithelial tumors are new growths, in the formation of 
which both vascular connective tissue and epithelial cells — that is, cells 
which are derived from either superficial or glandular epithelium — take 
part. The distribution of epithelium and connective tissue follows in 
general the normal arrangement of these tissues, the connective tissue 
either forming a basement structure whose surface is covered with epi- 
thelium (skin and mucous membranes), or forming a network or stroma, 
in the meshes of which the epithelial cells are disposed (glands). The 
imitation of the first-named structure leads to the formation of papillary 




Fig. 301.— Papillary epithelioma or ichthyotic wart of the skin (Muller's fluid, haematoxylin, eosin). a, 
Corium ; b, enlarged papillary body ; c, laminated homy layer, X 40. 

new=growths ; that of the second, to the formation of more or less 
sharply circumscribed nodules or to extensive superficial thickenings 
of tissue. 

According to the physical characteristics and grouping of the epi- 
thelial cells, as well as the clinical behavior of these tumors, epithelial 
new-growths may be divided into two groups ; one group including the 
24 



4:34 



TUMORS. 



papillary epitheliomata, adenomata, and cystadenomata ; the other 
the carcinomata and cystocarcinomata. The hi st groii]) is characterized 
clinically by the benign character of the growths, ivhicli are .sharply cir- 
cumscribed and form no metastases. The second grouxj, on tJic other hand, 
includes the inalignant new-growths, ir/ue// f/row by infi/tidtloii and give 
rise to metastases. The two groui^s, howe\ er, are not sharply separated 
from one another, as papillary epitheliomata and adenomata may, through 
changes in the mode of reproduction and the manner of spreading of the 
epithelial cells, become changed into carcinomata. 

(/>) Fax)iUary Epithelioma, Adenoma, and Cystadenoma. 

§ 119. A papillary epithelioma is a new-growth which is composed 
of a framework of connective-tissue i)apilhe covered with epithelial cells. 
In structure it is therefore similar to the papillie of the skin ; but the 
papillae of the new-growth are as a rule liigher and often branched, and 
the epithelial coA ering thicker. 

The papillary epithelioma of the skin occurs in the forjn of warty 
protuberances, which consist of slender papillae (Fig. 301) co\'ered with 
epithelium, the superticial layers of which show marked cornification 
(icJithyotic irarts and horny warts). These warts may, like the tleshy 
warts (see § 109), appear during childhood { Ichthyotic icarts) as well as in 
old age (verruca senilis). The first-named form represents a local mal- 




Fig. o02:— Senile horny wart of forehead, from a woman eighty-four years of age lalcohol, hiematoxy- 
lin, eosin). a. Cerium : 7>, epithelium ; c, atrophic sebaceous glands with development of horny epithelium 
in their ducts ; d, hypertrophic horny layers ; e, enlarged papillae. X 15. 



formation of the skin (Fig. 301) ; while the last-named is due to a patho- 
logical proliferation and cornification of the epithelium (Fig. 302, c, d) 
followed by an outgrowth of the papillae at the j)eriphery. An exces- 
sive cornification of the epithelium over hypertrophic papillte, giving 
rise to cylindrical or conical masses of horny cells in which, the horny 



PAPILLARY EPITHELIOMA. 



435 



layers lie at I'iglit angles to the surface of the skin, leads to the 
tion of a adaueous horn or coriiu cutaneuni (Figs. l!23 and 124). 

Papillary epitheliomata of the mucous membranes occur 
in the form of warty, nodular formations (Fig. 303, e, f), or in 
long, slender, papillaiy excres- 
cences (Fig. 304, a), which, 
springing from a narrow base, 
are often repeatedly branched. 
The former variety is found es- 
pecially frequently in the lar- /t/ 



forma- 

either 
that of 




FIG. 303 




Fig. 303.— Papillary epithelioma of tbe laryux. a. Epiglottis : 7), ossiried o icuicl cartilage ; c, thyroid carti- 
lage ; (/, trachea ; c, /, papillary proliferations. Natural size. 

Fig. 304.— Papillary epithelioma of the urinary bladder, a. Epithelioma ; h/c, enlarged prostate ; d, 
thickened bladder-wall. Five-sixths natural size. 



ynx, more rarely in the nose and urinary bladder ; the latter most frequent- 
ly in the urinary bladder and iDclvis of the kidney, vaginal portion of the 
uterus, and more rarely in the ureters, gall-bladder, and biliary passages.. 

In both cases the excrescences are formed of slender, connective -tissue 
papilla3 (Fig. 305) which contain blood-vessels, and are covered by a 
thick layer of epithelium. The character of the epithelium corresponds 
in general to that of the part in which the growth occurs, but papillomata 
covered with stratified squamous cells are sometimes seen in regions 
which normally possess cylindrical epithelium (nose). 

Papillary epitheliomata in dilatation=cysts, which are also called 
papillary cystomata, occur most frequently in cysts of the ovary and 
in cysts of the ducts of the mammarj' gland, more rarely in atlieromata 
(dermoids) of the skin. Within the cyst are formed small, warty ele- 
vations or cauliflower-like tumors, which under certain conditions may- 
fill the entire cyst- cavity. Their structure corresponds to that of the 



436 TUMORS. 

similar excrescences in papillary adenocystomata (see § 121), or the pap- 
illary epitheliomata of the skin aud mucous membranes. 

Papillary epitheliomata ot the surface of the ovary appear in foi nis 
similar to those of the urinary bladder, but are rare. Papillary epithe= 



Fig. 305,— Papillary epitlieliuiua uf the urinary bladder (alcohol, tijematoxylin, eosia). X 35. 

liomata of the cerebral ventricles take their rise in part from the telse 
choroideiB, and in part from the ex)endyma. 

It is difficult to draw a sharp line between papillary epitheliomata and otlier 
formations. In particular do those inflammatory proliferations of tlie si?;in and mucous 
membranes — tlie pointed condylomata — 'Wliich develop especially upon the external 
genitals under the influence of chronic irritations (compare Fig. 225), so closely resem- 
ble the epitheliomata thatj their inflammatory origin forms the only point of differ- 
ence. If the connective-tissue framework of the papillary outgrowths is developed 
to a greater extent than the epithelium, the tumor may be classed with the papillary 
fibromata, and it becomes a question of individual standpoint as to which designation 
shall be employed. Fioallj^ the benign papillary epitheliomata may pass over into 
carcinomata, either through the growth of the epithelium at the base of the papillae 
into the underlying connective tissue, or through the extension of the proliferating sur- 
face epithelium upon neighboring organs (as in the case of the papillary epitlieliomata 
of the ovary). In general, it may be said that the designation epithelioma is very often 
applied to carcinomaia (particularly in France), but it seems more expedient to reserve 
this term for the benign tumors described above. 

Among the epitheliomata may be classed those formations known as cholesteato- . 
mata or pearl tumors, which in part are caused by inflammation, and in part repre- 
sent misplaced embryonal tissue. The most striking characteristic of the cholesteatoma 
is the formation of glistening white pearls, which consist of thin, scale-like epithelial 
cells pressed closely together, and often inclose cholesterin. These tumors are found 
most frequently in the descending urinary passages, the cavities of the middle ear, and 
the pia of the brain ; very rarely in that of the spinal cord. 

Pathological cornifi cations, with the formation of glistening white scales and 
pearls, occur in the urinary passages, particularly in tlie course of chronic inflamma- 
tions. In the tympanic cavity, mastoid antrum, and external auditory canal, the chole- 
steatomata appear as yellowish-white or bluish-white nodules, varying in size from that 
of a cherry-stone to that of an egg, and presenting an onion-like laminated structure. 
Through their pressure upon the neighboring bone the.y may cause its disappearance. 
They arise as a product of squamous epithelium which lias penetrated from the ex- 
ternal ear through openings in the ear-drum into the cavities of the middle ear aud haa 





PAPILLARY EPITHELIOMA. CHOLESTEATOMA. 



437 



replaced the cylindrical epithelium, and under especial conditions (chronic inflamma- 
tions) produces the formations above described. It is probable that in rare cases they 
arise from epidermoidal cells which during tlie period of embrj^onic development have 
found their way into the cavities in question. 

The intracraiiial cholesteatomata are found at the base of tiie brain (very rarely in the 
spinal canal), in the region of the olfactoiy lobe, tuber cinereum, corpus callosum, in 
the choroid plexus, in the pons, medulla oblongata, and cerebellum. In these regions 
the cholesteatomata appear on the surface as silk-like, shining nodules of varying size 
which extend more or less deeply into the brain-substance. The nodules are single, 
but cholesteatoma-masses may become separated from the chief nodule and displaced 
into the neighboring tissue. According to Bositrom, it is always possible to demon- 
strate, at some point, a connection between the pia and the cliolesteatoma, where the 
scales composing the cholesteatoma take their origin from a cell-layer lying upon the 
vascular connective tissue, the cells of this layer throughout bearing the character of 
epidermoidal cells. The cholesteatomata of the pia may therefore be designated as 
cpitheliomata or as epidermoids {Bostrom) ; and their origin may be explained by the as- 
sumption that in the early period of development epidermal germs are misplaced into 
the anlage of the pia. According to Bostrom, this takes place in the time between the 
closure of the medullary canal and the separation (by a process of constriction) of the 
secondary vesicle of the fore-brain from the fore-brain or the 'tween-brain, and the separa- 
tion of the after-brain vesicle from the hind-brain (fourth to fifth week). These 
epidermoids may therefore be classed with the teratoid tumors (see Teratoma). 

Literature. 

(Fa^fyiUary Ejnthelmma . ) 

Albarran- Les tumeurs de la vessie, Paris, 1892. 
Berg-eng-riin : Verruca dura laryngis. Virch. Arch., 118 Bd., 1892. 
Hellmann: Papilloma durum d. Nasen- u. Stirnhohlcuschleimh. Arch. f. Laryng., 
vi., 1897 (Lit.). 

Hopmann: Warzengescliw. d. Respirationsschleinihaute. Klin. Yortr., No. 315, 
Leipzig, 1888. 

Israel: Epithelioma folliculare cutis. Festschr. d. Assist, f. Yirchow, Berlin, 1891. 
Kiirsteiner: Papillome u. Krebse d. Blase. Virch. Arch., 130 Bd., 1892. 
Kiister: Harnblasengeschwlilste. Saniml. klin. Yortr., No. 267-68. Leipzig, 1886. 
Lange: Papillome der Mundhohle. Deut. Arch. f. klin. Med., 40 Bd. 
Marchand: Zur Kenntniss d. Ovarientumoren, Halle, 1879. 

Pfannenstiel : Die papillaren Geschwiilste d. Eicrstocks. Arch. f. Gyn., 48 Bd., 
1895. 

Spietsclika: Histologic des Cornu cutaneum. Arch. f. Derm., 42 Bd., 1898. 
Stratz: Die Geschwiilste d. Eierstocks, Berlin, 1894. 

Tscliistowitscli: AVachsthum d. ZottenpoljqDcu d. Harn blase. Virch. x\rch., 115 Bd,, 
1889. 

Werner: Beitr. z. Kenntniss d. Papillome d. Kehlkopfs, Heidelberg, 1894. 
Williams: Papillomatous Tumors of the Ovary. Johns Hopkins Hosp. Rep., iii., 
Baltimore, 1892. 

Zarniko: Histologic d. Nasengeschwulste. Virch. Arch., 128 Bd., 1892. 

{Cholesteatoma. ) 

Beneke: Meningeale Cholesteatome. Virch. Arch., 142 Bd., 1895; 149 Bd., 1897. 
Beselin: Cholesteatomat. Desquamation im Niereubecken b. Tuberculose. Virch. 
Arch., 99 Bd., 1885. 

Bostrom: Die pialen Epidermoide, Dermoide u, Lipome u. duralen Dermoide. Cbl. 

f. allg. Path., viii., 1897 (Lit.). 
Chiari: Cholesteatome des Ruckenmarks. Prag. med. Woch., 1883. 
Glaeser: Untersuch. liber das Cholesteatom. Virch. Arch., 122 Bd., 1890. 
Gross: Contrib, a I'etude des tumeurs perles, Paris, 1885. 

Haug: Das Cholesteatom der Mittelohrraume. Cbl. f. allg. Path., vi., 1895 (Lit.). 
Nehrkorn: Meningeale Perlgescliwulst. Beitr. v, Ziegler, xxi., 1891 (Lit.). 
Thomas: Cholesteatomata of the Brain. Jour, of Med. Res., 1901 (Lit.). 
Virehow: Ueber Perlgeschwiilste. Virch. Arch., 8 Bd., 1855. 

§ 120. The adenomata are usually nodular tumors with sharply 
defined borders ; and are situated within glands, or in the skin or mucous 



438 



TUMORS. 



membranes. lu the latter situations they not infrequently appear in the 
form of polypi elevated above the surface. They may oeeiir also m the 



ft 



FTP S06 -Adenoma tuluilare (glandular polvp) of tlie intestine (alcohol aluni-carunne) a. Transverse 
FIG. 306. Adenoma^ tu ^^^^^^.^^^^^.^^^^ ^^^.^.^^^ aland-tubules ; c, stroma nrh m cells. X bU. 



form of papillary proliferations (Fig. 232). The al)senee of any tendency 
to grow by infiltration or to produce metastases stamps these growths as 

heniqn tumors. . ^ /• 7 7 

The chief characteristic of the adenoma is ihe fonnatiou of new glands, 
which depart more or less from the typical glands of thi^ affected organ. 



a;) -, 
c 



^1 



According to their structure adenomata may be classed as tuhidm- 
acinous; but these two fonns cannot be sharply separated, the one from 



ADENONA. 439 

the other. Through the formation of papillary excrescences on the inner 
walls of the gland-spaces there is formed an adenoma impiUiferum. 

The stroma snj)porting the glands consists in part of preexisting con- 
nective tissue, and in part of that which has been newly formed. 

Adenomata develop) either in normal tissue, malformed tissue, in tissues 
ichieJi hare been altered hy disease (inflamed mucous membrane, cirrhotic 




Fig. 308.— Adenoma mammae tubulare (alcohol, alum-carmine), a, Brancbed and dilated glandular spaces 
cut longitudinally ; &, same, cut transversely ; c, stroma. X 27. 

liver, contracted kidney, ovaries containing scar tissue), OTimm remains 
of foetal struetures (Wolffian body, canalis neure uteri cus, remains of 
enamel-germs). The new-formation of glands is dependent upon a pro- 



s- 

. *te-^ - J ..... . l^ ^ ..■ M . ... 

Fig. 309.— Adenoma mammge alveolare (alcohol, alum-carmine), a, Terminal alveoli; b, gland-ducts; c, 

connective-tissue stroma. X 27. 



liferation of the surface -epithelium or of glandular epithelium, the steps 
of this process being similar to those occurring in the regeneration of 

- ■ 



440 



TUMORS. 



normal gland tissue. The cause of the new-formation of gland tissue 
within normal organs is wholly unknown. Glandular new-formations 
developing in tissues which have been altered by inflammation, and 
which lead to tumor-like growths, may in the beginning bear the charac- 
ter of a regenerative or hyperplastic new-formation, and for this reason 
the adenomata cannot he sharply differentiated from regenerative and liyper- 
plastic proliferations. 

Tubular adenomata represent the most common form of the adeno- 
mata. They occur particularly in mucous membranes (Figs. 306 ; 307, / ) 
provided with tubular glands (intestine, uterus) ; but are found also in 
such glands as the breast (Fig. 308), liver, ovary, and not infrequently 
in the kidneys. They are characterized by the formation of simple and 
branched gland-tubules (Figs. 306, a, h ; 307 /; and 308, a, b) which are 
lined by simple columnar or cubical epithelium and form nodular tumors 
varying in size from that of a pea to that of an apple or a man's fist, or 
rarely even larger. 

The alveolar adenomata arise from glands (mamma, ovary, thyroid, 
sebaceous glands) ; and are characterized by the formation of numerous 
terminal berry-like alveoli (Fig. 309, a), as well as gland-ducts (&). 

Papillary adenomata arise through the formation within the tubules 
of an adenoma, of little elevations of epithelium into each of which a 
connective-tissue papilla grows. Through the extensive formation of 
such papillae the gland- tub ales may become wholly filled or even dilated 
(Fig. 310, h, c). 

The stroma of an adenoma is at times well developed, at other times 
but slightly, and consequently adenomata may be divided into hard 
(mammary gland) mid soft varieties (kidney, liver, ovary, testicle). An 




6 6 



Fig. 310.— Adenoma renum tubiilare papilliferuin (Miiller's fluid, haematoxylin). a, Connective-tissue 
stroma ; b, sinuous gland-tubules ; c, gland-tubules with marked development of papillary excrescences. 
X 27. 

especially marked development of the connective tissue leads to the for- 
mation of fibro=adenomata or fbrous adenomata. Such forms occur most 
frequently in the mammary gland. 

If, as happens not infrequently in the mammary gland, the connec- 
tive-tissue proliferation in an adenoma is not of a diifuse character but 
takes place particularly around the canaliculi (see Fig. 241), the tumor 



ADENOMA. 



441 



is ordinarily designated as a fibroma pericanalicular e. If, as the result 
of more marked local proliferative activity on the part of the connective 
tissue (Fig. 311, c, d, e), an ingrowth of rather broad and short papillse 




Fig. oil.— Fibroma intracanaliculare mammae (flbro-adenoma papilliferum) (alcohol, alum-carmine). 
«, Dense, Intercanalicular growth of fibrous tissue; h, pericanalicular tissue rich in cells; c, d, e, nodular, 
intracaiialicular connective-tissue proliferations cut longitudinally; /, intracanalicular proliferations cut 
transversely. X 23. 

(e) into the gland-spaces takes place, the resulting tumor is known as a 
fibroma intracanaliculare. According to its genesis such a tumor may 
also be appropriately designated a fibro=adenoma papilliferum. 

Adenomata cannot be sharply differentiated from tumor-liI?;e glandular hypertro- 
phies on the one hand, and carcinomata on the other. For example, in the healing of 
intestinal ulcers the regenerative processes in the glands may be so active as to give 
rise to polypoid formations, which may either be called glandular Jiypertrophies of the 
niucous membrane, or adenomata, according to the individual stancipoint. Likewise, 
different names may be applied to the glandular polypi which occur so frequently in 
the uterus. 

The carcinomatous nature of a new-growth resembling an adenoma (see § 122) is 
generally made evident by a more marked epithelial proliferation and by its infiltrative 
mode of growth. There are, however, adenomata, having a single layer of columnar 
cells, which grow by inliltration (particularly in the intestine), and thereby assume the 
character of malignant tumors. They should accordingly be classed with the carcino- 
mata, and must be designated either by the term adenoma destruens or adenocarcinoma. 
On the other hand, there are also adenomata with marked atypical epithelial prolifera- 
tion (mamma, endometrium), which — for a long time at least — do not show any malig- 
nant characteristics. 



442 



TUMORS. 



Literature. 

(Ad(')(()i))((. ) 

Barlow: Adenomata sebacea. Dent. Avcli. f. klin. Med., 55 Bd., 1895 (Lit.). 
Beneke: Leberadenom. Beitr. v. Ziegler, ix., 1891. 

Billroth: Tumoren der Brustdrlisen. Handb. d. Fraiienkraiikh., iii., Stuttgart, 1886. 
Bock: Ueber ein Adenoni der Talgdriisen, Berlin, 1890. 

Bonome: Contr. alio studio degli adenomi del legato. Arch, per le Sc. Med., xiii., 
1889. 

Brinaud: Du polyadenome gastrique. Arch. gen. de med., 1885. 
Eberth: Das Adenom der Leber. Virch. Arch., 43 Bd., 1868. 

Hauser: Polj^posis intestinalis adenomatosa. Deut. Arch. f. klin. Med., 55 Bd., 
1895. 

Hoffmann: Adenom der Leber. Virch. Arch., 89 Bd., 1867. 

Kelsch. et Kiener: Contrib. a I'hist. de I'adenome du foie. Arch, de phj's., 1876. 

Langhans: Ein Driisenpolyp des Ileums. Virch. Arch., 38 Bd., 1867. 

Leser: Beitr. z. path. An. d. Geschwiiiste d. Brustdrlisen. Beitr. v. Ziegler, ii., 1888. 

Menetrier: Des polyadenomes gastriques. Arch, de phys., i., 1888. 

Jfissen: Leberadenom bei Cirrhose. Inaug.-Diss., Freiburg, 1895. 

V. Noorden: Das verkalkte Epitheliom. Beitr. v. Bruns, 1888. 

V. Recklinghausen: Die adeuomyome ii. Cystadenome d. Uterus u. d. Tube, Berlin, 
1896. 

Ricker: Geschwiiiste der Niere. Cbl. f. allg. Path., viii., 1897. 
Bindfieisch : Leberadenoid. Arch. f. Heilk., v., 1864. 
Rovighi: Adenoma racemoso del legato. Arch, per le Sc. Med., vii., 1883. 
Simmonds: Die knot. Hyperplasie u. d. Adenom d. Leber. Arch. f. klin. Med., 34 
Bd., 1884. 

Steudener: Adenom der Brustdrlisen. Virch. Arch., 42 Bd., 1868. 
Sturm: Ueber das Adenom der Niere. Arch. d. Heilk., xvi., 1875. 
Weichselbaum u. Greenish: Adenom der Niere. Wiener med. Jalirb., 1883. 
Weigert: Adenocarcinoma congen. renis. Virch. Arch., 67 Bd., 1876. 
See also 119 and 121. 

§ 121. A cystadenoma or adenocystoma is an adeyioma whose gland- 
spaces have undergone cystic dilatafion through the accmnulation of secretions. 

Such tumors are usually com- 
posed of numerous cysts, and 
are, therefore, designated as 
niultilocular cystomata. Ac- 
cording to the character of the 
cyst -wall there may be distin- 
guished a smooth-tvalled or simple 
cystoma {cystoma simplex), or a 
papiUiferous cystoma (cystoma pap- 
illiferum). 

Small amounts of secretion 
are often seen in the ordinary 
adenomata (Fig. 306), and the 
spaces of both simple and pap- 
illary adenomata are often so 
wide (Figs. 308, 311) that 
they at once attract the eye on 
cross- section of the growth. In 
cystadenomata such cyst-forma- 
tion is the predominating feat- 
ure. 

The early stages of the cysts are represented by gland-tubides of vary- 
ing shape (Figs. 312 and 313, b), which lie in a more or less richly 
developed connective-tissue stroma. Through the accumulation of secre- 




CYST ADENOMA. 



443 



tiou tliese tubules become gradmilly dihited so that numerous small cysts 
arise (Fig. 314), or else both large aud small cysts (Figs. 315-319) are 




Fig. 313.— Adenocystoma of the bile-passages in tiie first stages of development (alcohol, hsematoxylin) . 
a. Liver tissue ; h, adenoma tissue In the periportal connective tissue. X 90. 

formed. Often the relationship is such that the tumor mav consist of a 
few large cysts (Fig. 318) in whose walls smaller cysts occur; or there 




Fig. 3U. Fig. 315. 

Fig. 314.— Section of a portion of a multilocular adenocystoma of the ovary. Reiluced about one-sixth. 
Fig. 315.— Section through an adenocystoma of the testis of a four-year-old boy. Natural size. 



4:U 



TUMORS. 





3ft 




/ 



^ f 



r 



-P.p qifi-Miiltilocular adeuuevMoiiia of the liver, seen in section, a. Liver parenchyma: iij^^m- 
FIG. dib. Miuiuocuidi aueuuL.>.-L 1 ^ smaller cysts, separated from each other 



branous margin of the left lobe ; c, d, large cysts ; e, group 



onTrby cZkective tissue ; f, portal vein fy, hepatic artery. Two-thirds natm-al size. 





FIG. 317.-Cystoma of the kidney, cut transversely. Eleven-fourteenths natural size. 



CYSTADENOMA. 



445 



may be found, by the side of large cysts (Fig. 316, <?), portions of tissue, 
which contain only small cysts (e) or even appear solid— that is, consist- 
ing of a tissue the glands of which are not dilated. 




Fig. 318.— Adenocystoma ovarii partim simplex, partim papilliferum, a. Smooth-walled cysts ; h, soft 
papillary growth covered with simple, mucous-forming cylindrical epithelium. (Metastatic nodules were 
present in the peritoneum.) Reduced one-third. 

All the different varieties of cystomata may develop in the ovaries 
(Figs. .314 and 318), testicles (Fig. 315), liver (Figs. 313 and 316), kid- 
neys (Fig. 317), and the mammary glands. 




Pig. 319.— Portion of a papillary adenocystoma of the ovary, seen in section. (Drawn from a specimen 
hardened in chromic acid.) Four-flfths natural size. 



446 TUMORS. 

In the ovaries cystomata not infrequently develop coincidently on 
both sides, and may be associated with dermoid formations. Adenocj s- 
tomata of the testicles not infrequently inclose within their stroma foci 
of cartilage or other tissue, so that such growths should be classed with 
the teratomata (§ 129). 

The epithelial lining of cystomata is usually composed of simple colum- 
nar cells, but may be a ciliated, cubical, or flattened epithelium. 

The cyst- contents usually consist of a clear, often distinctly ropy fluid, 
which contains a mucin-like substance (pseudomucin, see § 60). This 
substance is a product of the epithelial lining in which goblet-cells are 
often found (Fig. 320, c). ^Tot infrequently the fluid also contains whit- 
ish flakes, the products of cells which have undergone fatty degeneration ; 
or it may be more or less cloudy or reddish or brownish from previously 
occurring hsemorrhages. An abundant secretion in many cysts may lead 
to the formation of tumors of enormous size ; in the ovary, for example, 
fhey may reach a weight of from ten to tvv^elve kilograms or more. 

The papillary adenocystomata constitute a common variety of adeno- 
cystoma. They are characterized by the fact that sooner or later pai^il- 
lary excrescences develo]) in the glands which have undergone cystic 
degeneration. 

In the adenocystomata of the ovary these excrescences are usually 
slender and delicate, forming villous-like outgrowths (Fig. 319) or cauli- 




Pm. 320.— Cystoma papilliferum ovarii (Miilli^r's fluid, hematoxylin, eosin). a, Stroma with papillae; 
b, Rland-tubule with small papilla? ; c, high ci'lindrical epithelium; c/. mucus containing cells, within the 
cyst-spaces. X 150. 



flower elevations, which may fill up a larger or smaller part of the cysts. 
Minute papillary elevations, extending over an extensive area of the 
inner surface of the cyst- wall, may give to the latter a velvety appear- 



PAPILLARY CYSTADENOMA. 



447 



ance similar to that of a mucous membraue. If the excresceuces develop 
in cysts of small size, they may fill these, and the tissue may thereby take 
on the appearance of a dense, n on -cystic, medullary tumor, though from 
the cut surface more or less mucus can usually be obtained. 

Larger papillae are always more or less branched (Fig. 320), and con- 
sist of a cellular stroma («), whose surface is usually covered with tall 




FIG. 321.— Papillary adenocystoma of the ovary with myxomatous degeneration of the connective tissue 
of the papillae (Miiller's fluid, hiematoxylin). a, Fibrous stroma; b, papillse which have undergone 
myxomatous change ; c, epithelium. X 80. 

columnar cells (c) of the character of goblet-cells. The contents of the 
cysts consist of ropy mucus (d) mingled with more or less numerous 
descpiamated cells which have undergone mucous degeneration, or the 
remains of such cells. In rare cases the connective tissue of the i)apill8e 
may undergo a mucous degeneration (Fig. 321, a, h), and may swell to a 
marked degree, and finally become changed into myxomatous spheres 
covered externally with epithelium. 

Adenocystomata of the liver, testicles, and kidneys usually form no 
papillae, or at most very small ones. In the i3apillary adenocj stomata of 
the mammary gland the excrescences are usually broad and plump (Fig. 
322), as is the case with those of the papillary adenomata (Fig. 311). 
Accordingly, on the cross-section of such tumors the cyst-spaces are found 
to be filled with i3olypoid proliferations of various forms (Fig. 322), 
which are often flattened through mutual pressure, and give to the sur- 
face of such a cross-section a laminated appearance. 

Since in these tumors the connective-tissue elements predominate over 
the epithelial, these growths are often classed with the connective-tissue 
tumo)'s, and designated, according to the character of the connective tis- 
sue, as cystofihyoma, cystoniyxoma, or cystosarcoma. When showing a 
structure of leaf -like layers they have received the name of sarcoma 
phyllodes. 

The papillary adenocystomata show a certain malignancy, even when 
the papillse are covered with a simple epithelium (see cj^stocarcinoma). 



448 



TUMORS. 



This is shown in the first i)hice, in the fact that the ])ai)i]laiy piol iter- 
ations may break through the eyst-wall, in the case of such tiuuois of 
both the ovary and nianiuuiry ghiud, and in the hitter situation they may 




Fig. 323.— Papillary cystoma or intracanalicular papillary tlbroina of the bi east, laid open by a longi- 
tudinal incision. One-half natural size. 

also break through the skin. Papilhiry ovarian cystoniata (Fig. 318, b) 
may in this way give rise to metastases in the peritoneal cavity, and 
these in turn display the characteristics of ]3apillary epitheliomata. 

The ademcystoniata represent a variety of tumor which possesses no sharpl}' defined 
limits ; for example, papillary cystomata may arise from the development of papillary 
excrescences in dilatation-cysts which are formed from pre-existing glands (see >5 119). 
Farther, malformations of organs— for example, of the kidneys — may lead to the 
formation of multilociilar cystomata, the cystic dilatation affecting not only the urinary 
tu])ules, but also Muller's capsules. That teratomata ma}' appear in the form of 
adenocystomata has already been mentioned in the text. Finally, a transition from 
cystadenoma to cystocarcinoma may also take place. 

Literature. 

{Adenocystoma.) 

Bard et Lemoine : La maladie kystique essent. des organes glandulaires. Arch. gen. 
de med., 1890. 

Baumgarten : Ovarialkystom mit Metastaseu. Virch. Arch., 97 Bd., 18S4. 
Billroth: Handb. d. Frauenkrankheiten, iii., Stuttgart, 1886. 

Bdttcher: Entwickelung mtiltilocularer Eierstockscysten. Virch. Arch., 49 Bd., 1870. 
Brissaud: Maladies kystiques de la mamelle. Arch, de phys., iii., 1884. 
Brodowski: Mit Flimmerepithel ausgekleidete Ovarialcysten. Virch. Arch., 67 Bd., 
1876. 



CARCINOMA AND CYSTOCARCINOMA. 



449 



Burckhardt: Genese d. multilocul. Ovarialcysten. Vircli. Arch., 144 Bd., 1896. 
Coblenz: Kystome der Ovaneu. Zeitsclir. f. Geb. u. Gyu., vii., 1882; Genese u. 

Eut wk'kelung von Kystomen. Vircb. Arch., 84 Bd., 1881. 
Dinochowski ii. Janowski: Totale cystische Entartung d. Leber. Beitr. v. Ziegler, 

xvi. , 1894. 

Flaiscblen: Multiloculare Fbrnmerepithelkystome der Ovarien. Zeitschr. f. Gvn., 
vi., 1881. 

Goebel: Kiefertumoren v. Zahnsystem ansgehend. Cbl. f. allg. Path., 1897 (Lit.). 

Hess: Ueber eine subcutane Flimmercyste. Beitr. v. Ziegler, viii., 1890. 

V. Hippel: Multiples Cystenadenom der Gallengange. Virch. Arch., 123 Bd., 1891. 

Israel: Epithelioma folliculare cutis. Festschr. d. Assist, f. Virchow, Berlin, 1891. 

V. Kahlden: Genese der multiioc. Cystenniere u. d. Cystenleber. Beitr. v. Ziegler, 
xiii., 1893; Congen. Adenoni beider Nieren. lb., xv., 1894; Entsteh. d. Ovarial- 
cysten. lb. xxvii. 1900. 

Kocher: Die Krankheiten des Llodens, Stuttgart, 1882. 

Labbe et Coyna: Traite des turn, beuignes du sein, 1876. 

Leser: Beitr. z. pathol. Anatomic d. Geschwiilste d. Brustdrusen. Beitr. v, Ziegler, 
ii., 1888. 

Malassez: Maladies kystiques du testicule. Arch, de phys., 1875. 
Marcband: Beitr. z. Kenntniss der Ovarialtumoren, 1879. 
Michalowicz : Degenerescence kystique des reins et du foie, Paris, 1877. 
Monod et Terillon: Traite des maladies du testicule, Paris, 1889. 
Nag-el: Genese der epithelialen Eierstocksgeschwiilste. Arch. f. Gyn., 33 Bd., 1888. 
Nauwerck u. Hufschmid: Leb. d. multilocul. Kystome d. Mere. Beitr. v. Ziegler, 
xii., 1892. 

Olshausen: Die Krankheiten d. Ovarien. Handb. d. Frauenkrankheiten, ii., Stutt- 
gart, 1886. 

Pfannenstiel : Die Pseudomucine der cystischen Ovarialgeschwulste. Arch. f. Gyn., 
38 Bd., 1890; Neubildungen des Eierstocks. Handb. d. Gynak. v. Veit, iii., 1898. 
Rug-e: Papilliformes Atherom. Virch. Arch., 136 Bd., 1894. 

Sabourin: Degenerescence kystique du foie et des reins. Arch, de phys., x., 1882. 
Sasse: Cj^sten u. cystische Tumoren der Mamma. Langenbeck's Arch., 54 Bd., 1897. 
Schmidt: Cystosarkom der Mamma. Arch. f. Gyn., xxii., 1884. 

de Sinety et Malassez: Sur la structure, I'origine et le developpement des kystes de 

I'ovaire. Arch, de phys. , 1878, 1879, 1880, 1881. 
Spiegelberg: Driisenschlauche im fotalen Eierstock. Virch, Arch., 30 Bd., 1864. 
Stratz: Die Geschwiilste des Eierstocks, Berlin, 1894. 

Terburgh: Ueber Leber- u. Nierencysten. Inaug.-Diss., Freiburg, Leiden, 1891. 

V. Velits: Genese der Flimmerepithel-Kystome des Eierstocks. Zeitschr. f. Geb., 

xvii. , 1891. 

Zoppritz: Multiloculare Kiemengangscysten. Beitr. v. Bruns, xii., 1894. 
See also ^ 120. 

(c) Carcinoma and Cystocarcinoma. 

§ 122. The carcinomata are malignant epitheliaJ tumors characterized 
by inJiUrative growth and thefonnation of metastases. 
They develop : 

(1) In the skin, mucous membranes and in glands, all of which ap- 
peared to be normal, before the development of the carcinoma. 

(2) In the skin, mucous membranes, and in glands, which have 
already suffered changes before the development of the carcinoma. 

(3) In already existing papillary epitheliomata, adenomata and ade- 
nocystoma ta. 

(4) From the remains of foetal epithelial structures, and from epithe- 
lial tissues which have been misplaced through disturbances of develop- 
ment, and have already developed into pathological formations. 

(5) From the epithelial tissues of the chorionic villi and placenta. 
The most essential characteristic of the development of a carcinoma 

is that presented by atypical proliferations of epithelium which sooner 
or later penetrate into the tissue bordering upon the affected glands 
or surface=epithelium. This phenomenon is usually accompanied by a 
proliferation of connective tissue ; but this is not absolutely essential 



450 



TUMORS. 



to the development of a carcinoma. The tissue invaded by the epithelial 
proliferation — whether glandular tissue, muscle, bone, etc. — is sooner or 
later destroyed by the growth. 

The cause of the atypical growth of epithelium is not known with 
certainty ; it can only be said that certain conditions favor such growth. 
Thus, for exam]3le, old age predisposes to the develoi:)ment of carcinomata 
of the skin, inasmuch as in this period of life the connective tissue of the 
skin undergoes a certain amount of atrophy and becomes looser in struct- 
ure, while the epithelium, at least in part, continues to increase, and 
under certain conditions shows here and there distinct evidences of 
increased activity (formation of heavier hairs upon the nasal septum, 
lobes of the ears, and in the eyebrows). Likewise carcinomata of the 
mucous membranes and the glands usually ai)pear in the later years of 
life, although they may occur earlier in life, even in childhood. 

Further, the misplacement and separation of epithelium predisposes to 
the formation of cancer. Such condition may easily happen during the 
healing of ulcers, and also at the borders or on the surface of both infec- 
tious and non-infectious growths of granulation-tissue. Consequently 
carcinomata not infrequently arise in ulcers^ scars, infective granuloniata 
(for example, in tuberculous lujius of the skin and mucous membranes), 
or in tissues ivMch have been changed by in flammation of any kind (for exam- 
ple, in a cirrhotic liver). 

All these predisposing factors do not constitute the unique cause of 
the development of a carcinoma. They ms.y exist for a long time with- 
out giving rise to a cancer. It appears that something else must be 
added to cause the unlimited atypical proliferation of epithelium, and 
what this something is, is at present unknown. 

In recent years the opinion has been many times advanced and main- 
tained that parasites cause carcinomatous and sarcomatous prolifer- 
ations. But the majority of the appearances which have been described 
as parasites (as protozoa, especially sporozoa, and as yeast-fungi) have 
not been parasites at all, but degenerated nuclei and nuclear division- 
figures, or leucocytes inclosed within tumor-cells, or degeneration-i3rod- 
ucts of such, or products of cell-protoi)lasm, particularly keratohyalin 
and colloid, or epithelial hyalin and mucin. In the few cases in which 
true parasites were present in the tissues, this occurrence could very well 
have been a secondary infection, which in no way could be regarded as a 
cause of the development of the tumor. In not a single case has it been 
py^oved beyond all doubt that parasites have been the cause of either carcinoma 
or sarcoma. 

Certain portions of the intestinal tract — the rectum, the flexures of 
the colon, the pylorus and cardia of the stomach, the oesophagus, 
pharynx, tongue, and gums — are favorite seats for the development of 
cancer. Cancer may develo]3 in any portion of the skin, but it occurs 
more frequently on the lips and nose than on the remaining portions of 
the face, or on the extremities, and on these again more frequently than 
on the trunk. Of the sexual apparatus the parts most commonly affected 
are the mammary gland and cervical portion of the uterus ; less fre- 
quently, though relatively often, the ovary, testicles, body of the uterus, 
vulva, vagina, and penis. The liver, kidneys, bladder, trachea, bronchi, 
lungs and pancreas occupy a middle ground; while the larynx and 
gall-bladder are, on the other hand, more frequently affected. 

Cancer usually develops in the form of nodules, ichich are not sharply 
differentiated from the neighboring tissues; on the mucous membranes 



CARCINOMA. 



451 



they are not infrequently elevated above the surface in the form of 
sponge-like, or polypoid, or papillary grotvths. From the point of origin 
tliey spread by an infiltrative growth of the epithelial proliferations, 
by which either the nodules increase in size or there are formed diffuse 
superficial thickenings, as in the case of the intestinal wall. The ovaries, 
testicles, uterus, kidneys, etc., may be partly or wholly transformed into 
carcinomatous tissue. Often the boundaries of the organ originally 
affected are overstepped, and the epithelial infiltration extends into 
neighboring tissues and organs. Thus, for example, a carcinoma of the 
mamma may infiltrate the neighboring fat, skin, and muscle; one of the 
gums, the maxillary bone ; one of the uterus, the vagina, parametrium, 
bladder, and rectum; a cancer of the gall-bladder may involve the liver; 
one of the thyroid, the trachea; and one arising in the bronchi, the 
lungs, etc. 

The formation of metastases may take place either through the 
lymph- or blood-vessels, and is of very frequent occurrence by both 
routes. It leads to the development of secondary nodules in different 
organs; but it may hapi)en that large lymphatic areas — as, for example, 
the lymphatics of the lung — may be simply dilated by the new-growth, 
without the formation of circumscribed nodules. The transportation of 
cancer-cells to the bone-marrow may lead to a carcinomatous degener- 
ation of the marrow of an entire bone or of several associated bones. 
Moreover, it should be noted that probably not every transportation of 
cancer- cells is followed by the development of a cancer, but that many 
of the cells so transplanted die. 

The tissue of a carcinoma is sometimes white and soft like marrow, 
sometimes fii^m and dense ; but it is almost always possible to obtain from 
the cut surface more or less of a whitish, cloudy fluid called cancer juice 
or cancer fnilJc. Very often the cut surface presents a tough, fibrous 
framework in the meshes of which the softer masses lie ; and from which 
the latter may be squeezed out by pressure either in the form of fluid, or 
as plugs or as crumbling masses. 

The masses obtained from the cut surface through pressure and scrap- 
ing consist, for the chief part, of atypically proliferating epithelial 
cells, the so-called cancer=cells, which are found in a great variety of 
forms, and usually show degenerative changes, particularly fatty de- 
generation. A true secretio7i of these epithelial cells is usually not 
found; but cancers occur — particularly in the mucous membranes, 
ovaries, mammary glands, and thyroid — which produce mucin, pseudo- 
mucin, or colloid. The amount of secretion may at times be so abundant 
as to lead to the formation of cysts and thereby to cystocarcinoma. 

Retrograde changes occur very often in cancers at an early stage. 
They are caused partly by the feeble vitality of the new-growth, partly 
by circulatory disturbances, which may be due to the filling -up of capil- 
laries and veins by the ingrowing cancer-cells, and partly by external 
causes. These changes lead, in the first place, to a destruction of cancer- 
cells in certain portions of the tumor, so that, after resorption of the dead 
material, the tissues often sink ia, and in this way depressions are caused 
over the surface of the tumor-nodules. Such depressed areas are seen 
I)articularly upon primary cancer-nodules in the mammary gland, and 
on secondary nodules in the liver, lungs, and other internal organs, and 
are often spoken of as cancer -umMlications. 

The retrograde changes often lead to complete destruction of tumor - 
tissue, and thereby to the formation of ulcers. This occurs particularly 



452 



TUMORS. 



in cancers of the mncons membranes, these growths at the patient's 
death nsnally revealing a more or less extensive ulceration ; but such 
ulcerations also take place in carcinomata of the mammary glands and 
skin. In the latter situation the cancer may take on the api^earance of 
a rodent ulcer. The edge of such ulcers is sometimes elevated and re- 
sembles a wall, or it may be studded with nodules ; at other times it is 
more sharply defined and only slightly infiltrated. The base of the ulcer 
is sometimes fissured and ragged, and covered with necrotic tissue ; at 
other times it is smooth. 

The question as to the etiology of carcinoma and sarcoma has led in recent 
years to numerous histological and experimental investigations, and publications in 
this line have been made by Sanfelice, Aievoli, Secchi, Flimmer, Wlaeff, Sjdbi'ing, 
Schilller, Curtis, Leopold, Fabre-Domergue, Petersen and Exner, Sternherg, and others. 
While the earlier writers believed that sporozoa were to be regarded as the cause of 
carcinoma and sarcoma, recent investigators have sought to prove the etiological rela- 
tionship of yeasts or rhizopods (Sjobring). Against these views, I believe, in common 
with Fabre-Domergue, Sternberg, Petersen, and Exner, that many of the formations 
which have been described as yeasts were not such, but wei-e cell-products resembling 
them. 

Likewise, the appearances described as protozoa are of a very doubtful nature. 
Sjc>bring ^Q^CYihG^ them as very delicate, clear bodies which cannot be fixed ; Schilller, 
as large, round, bladder-like bodies of a gold-yellow or brownish color. 

The results of attempts at cultivation and of animal exjDeriments have shown only 
that, outside of the human body, perhaps also by chance in tumors, there are forms of 
Saccharoinycetes {Saccharornyces neoformans of Sanfelice), which when injected into ani- 
mals cause inflammations and proliferations of granulation-tissue, and in part also pro- 
gressive diseases leading after weeks or months to death. The statements of V>l<i(ff, 
Leopold, Sanfelice, and others, that they have also produced true tumors, adenomata, 
adenocarcinomata, carcinomata, and sarcomata, give rise to well-founded doubts con- 
cerning the correctness of their interpretations, inasmuch as the appearances described 
may very well have been inflammator}' proliferations within which glands have also 
proliferated (intestinal glands, bile-ducts). The assertion of Leopold that he had been 
able, through the injection, into the testicle of a rat, of yeasts cultivated from an ovarian 
cancer, to produce a giant-celled sarcoma in the form of multiple nodules in the peri- 
toneal cavity of the animal, can hardly be taken as evidence of the parasitic nature of 
cancer. Likewise, the statement of Sjobring that he had been able to produce in four 
mice, by means of rhizopods, a cylindrical-celled and squamous-celled carcinoma, a 
colloid cystoma, and an adenoma of the sebaceous glands respectively, is of no value, 
because of the meagreness and inaccuracy of his description. 

Literature. 

{Etiology of Carcinoma. ) 
Alberts: Das Carcinom, Jena, 1887. 

d'Anna: L'eziologia del cancro. II Policlinico, Roma, 1894. 

d'Arcy : Some Effects of Chronic Irritation upon Living Tissues. British Med. Journ., 
ii., 1893. 

BinagM: Blastomyceten in Epitheliomen. Zeitschr. f. Hyg., xxiii., 1896 (Lit.). 
Borrel: Sur la signification des figures decrites comme coccidies. Arch, de med., ii., 
1890. 

Bosc: Le cancer, mal. infect, a sporozoaire. Arch, de phj^s., x., 1898. 
Broscli: Genese der malignen Geschwiilste. Virch. Arch., 162 Bd., 1900. 
Burchardt: Ein Coccidium im Schleimkrebs des Menschen. Virch. Arch., 131, 1893. 
Chaintre: De I'epithelioma des cicatrices. Lancet, ii., 1889. 

Claessen: Ueber die in Carcinomzellen gefundenen Einschllisse. Beitr. v. Ziegler, 
xiv., 1893. 

Clarke: Observat. on the Histol. of Cancer. Cbl. f Bakt., xvi., 1894. 
Debenedetti : Eziologia del cancro, Torino, 1887. 
Fabre-Domergue: Les cancers epitheliaux, Paris, 1898. 

Firket: De I'origine du cancer. Ann. de la Soc. beige d. microsc, xvi., 1891. 
Foa: Sui parassiti et suUa istologia patologica del cancro. Arch, per le Sc. Med., 
xvii. ; Arch. ital. de biol., xx., 1893. 



DEVELOPMENT OF CARCINOMA. 



453 



Foulerton: Pathogenic Action of Eiastomycetes. Journ. Path, and Bact., 1899. 

Gaylord: The Protozoon of Cancer. Amer. Journ. of Med. Sc., 1901. 

Greenough: Plimnier's Bodies in Carcinoma. Journ. Bost. Soc. Med. Sc., 1900; Cell 

Inclusions. Journ. of Med. lies., 1902. 
Hauser: Das cliron. Mageugeschwiir, sein Vernarbvmgsprocess u. dessen Be-zi.eh. zum 

Magencarcinom, Leipzig, 1883; Das Cylinderepithelcarcinom d. Magens U. d. 

Darms, Jena, 1890. 
Karg": Ueber das Carcinom. Deut. Zeitschr. f. Chir., 34 Bd., 1892. 
Lack: Experim. Production of Cancer. Journ. of Path., vi., 1899. 
Le Count: Analogies Between Plimmer's Bodies and Certain Structures found Kor- 

mally in the Cj^toplasm. Journ. of Med. Res., 1902. 
Leopold: Aetiologie d. Carcinoms. Arch. f. Gyn., 61 Bd., 1900. 

V. Leyden u. Schaudinn: Leydenia gemmipara. Sitzber. d. Akad. d. Wiss., Berlin, 
1896. 

Liebe: Ueber den Paraffinkrebs. Schmidt's Jalirb., 236 Bd., 1892. 

Nepveu: Rech. hist, sur la pathogenic du cancer. Marseille med., 1892. 

Nichols: First Annual Report on the Etiology of Cancer. Journ. Bost Soc. Med. 

Sc., 1900; Second Report. Journ. of Med. Res., 1902. 
Petersen u. Exner: Hefepilze u. Geschwulstbildung. Beitr. v. Bruns, xxv., 1899. 
Pfeiffer : Untersucliungeu liber den Krebs, Jena, 1893. 
Pianese: Beitr. z. Histologic u. Aetiologie d. Carcinoms, Jena, 1896. 
Plimmer: On the Etiology and Histolog}^ of Cancer. The Practitioner, 1899, 1900. 
Roncali: Aetiologie des Krebses. Cbl. f. Bakt., xxi., 1897. 
Rosenthal: Mikroorgauismen in Geschwiilsten. Zeitschr. f. Hyg., v., 1889. 
Ruifer: Les parasites des turn, epitheliales, Traite de path, gen., ii., Paris, 1896. 
Rufier and Plimmer: Parasitic Protozoa in Cancerous Tumors. Journ. of Path., i,, 

1892; ii., 1893. 

Sanfelice: Wirkung d. Blastomyceten, Zeitschr. f. Hyg., xxi., 1895; xxii., 1896; 
xxix., 1898. 

Schiiller: Zur Aetiologie d. Geschwiilste. Cbl. f. Bakt., xxvii., 1900. 
Schiitz: Protozoen- u. coccidienart, Mikroorganismeu in Krebszellen. Miinch. med. 
Woch., 1890. 

Schulthess: Statist. Unters. lib. d. Aetiologie d. Mammacarcinonis. Beitr. v. Bruns, 
iv., 1881. 

Schwarz: Ueber den Carcinomparasitism us, Wien, 1895. 
Sjobring-: Mikroorgauismen in Geschwiilsten. Cbl. f. Bakt., xxvii., 1900. 
Steinhaus: Ueber Carcinomeinschllisse. Virch. Arch., 126, 127 Bd., 1891. 
Sternberg": Zelleinschllisse in Carcinoraen. Beitr. v. Ziegler, xxv., 1899 (Lit.). 
Steven and Brown: On the So-called Parasitic Protozoa of Cancer. Journ. of Path., 
ii., 1893. 

Strobe: Histogenese ti. Aetiologie des Carcinoms. Cbl. f. allg. Path., ii., 1891 (Lit.); 

Die parasitaren Sporozoen in iliren Bezieliungen zur menschl. Pathologic, insbes. 

zur Histogenese u. Aetiologie d. Carcinoms. lb., v., 1894 (Lit.). 
Thoma: Parasitiire Organismen in d. Epithelzellen d. Carcinome. Fortschr. d. Med., 

vii., 1889. 

Volkmann: Ueb. d. primiiren Krebs d. Extremitaten. Samml. klin. Vortr., No. 
334-335, 1890. 

Wlaeff: Role des Blastomycetes dans I'organisme. Soc. An. Paris, 1900; Cbl. f. allg. 
Path., 1900. 

Zenker: Der primare Krebs der Gallenblase u. seine Beziehung zu Gallensteinen u. 
Gallenblasennarben. Deut. Arch. f. klin. Med., 44 Bd., 1889. 

§ 123. The development of carcinoma of the skin takes place most 
often from the surface ejntheUiwi, and is characterized essentially by the 
growth of the interpapillary portions of the same into the deeper por- 
tions of the skin, in the form of epithelial pings (Fig. 323, d) which fill 
up the connective-tissne spaces. The stratum corneum (c) may also 
undergo hypertrophy along with the cells of the rete Malpighii, and 
penetrate into the deeper tissues with the epithelial plugs (d). More- 
over, the horny cells which get into the deeper tissues may form epithelial 
pearls (e). 

Besides the surface-epithelium, the epithelium of the hair-foUicles and 
sebaceous glands may also take part in the development of the cancer ; 
and there occur carcinomata of the skin, which develop entirely from 



454 



TUMORS. 



the sebaceous glands, and therefore should be classed with the gland- 
cancers. 

The connective tissue may remain entirely passive dnring the ingrowth 
of the epithelinm, bnt is sooner or later excited to growth (Fig. 324, a), 
and the papillie often de^^elop into long, branched formations (/). In 




Fig. 323.— Transverse section through a carcinoma of the lip (alcohol, htematoxylin, eosin). a, Cerium, 
in a state of proliferation ; epitljeliiun ; c, thickened horny layer ; d, epithelial plugs extending into the 
corium ; e, epithelial plugs with horny pearls, cut obliquely ; /, enlarged papillae. X 13. 



the proliferating connective tissue there are often found in association 
with the flbrohlasts also Jeucocytes, which may penetrate into the epithe- 
lium. They become especially numerous in the event of tissue-destruc- 
tion, so that under such circumstances the proliferation of the connec- 
tive tissue acquires wholly the character of an inflammatory granulation 
tissue. 

The origin of the carcinomata arising from mucous membranes 
covered with squamous epithelium may be the same as that of a can- 
cer of the skin — that is, it is introduced by a proliferation of the surface 
epithelium (Fig. 324, a, c). If glands are present they may also take part 
in the development of the cancer. It is a remarkable fact that in the for- 
mation of such a tumor, glands with cylindrical epithelium may furnish 
epithelial products which correspond with those of the surface -epithe- 
lium. The epithelial proliferation may at first be intracanalicular and 
lead to a diffnse thickening and stratification of the epithelium (Fig. 
324, or to the formation of excrescences {e). Later, the proliferating 
epithelium breaks into the connective tissue. 

The connective tissue behaves in the same manner as in the case of 
cancer of the skin. 

The cylindrical=celled carcinomata of the mucous membranes arise 
in the case of the intestine from the tubular glands or from the crypts, the 
epithelium of which at first undergoes an acti^^e proliferation, and be- 
comes stratified, while the glands become dilated (Fig. 325, h). Later, 
the glands become changed into branching, atypically formed structures 
(c), which possess an epithelium arranged in many layers, and which 
grow into the neighboring tissues. 

In the stomach the gastric glands change their character (Fig. 326, 
/), and then through a continued growth infiltrate the submucosa {g), 
the muscularis {d), and the serosa (e). 



DEVELOPMENT OF CARCINOMA. 



455 



The epithelium of the newly -formed glands stains more deeply with 
nuclear stains than does normal epithelium. 

The connective tissue, as in the case of cancer of the skin, sooner or 
later proliferates, and in connection with this proliferation there may 
occur also an emigration of leucocytes. 

The development of cancer in glands— as, for example, in the mam- 
mary gland — likewise begins with an epithelial proliferation, as the result 
of which the glands (Fig. 327, a) become widened, altered in form (b), 
while their lining epithelium becomes stratified (b). With the breaking 
through of the epithelium into the neighboring connective-tissue spaces, 
the epithelial infiltration of that tissue is begun. According to the 
structure of the gland in which the cancer arises, and according to the 




Fig. 334.— Beginning development of carcinoma in the vaprinal portion of the uterus (alcohol, Bismarck- 
brown), a. Epithelium; b, connective tissue ; c, surface epithelium growing into the deeper tissues; (7, 
dilated glands ; c, glandular epithelium growing out in form of plugs ; f , cross-section of a gland, the 
cylindrical epithelium of which has become converted into stratified epithelium. X 45. 

variety of the cancer itself, there will be produced varying microscopical 
pictures. 

The connective tissue of the gland through j)roliferation also takes 
part in the building-up of the tumor ; but in the early stages of develop- 
ment such proliferation may be slight or entirely wanting. 

The development of a carcinoma in an adenoma or fibro adenoma 



456 



TUMORS. 



(Fig. 328, a) is likewise iiiiliated by a i/io)^' aciire proHu ndion of the epi- 
thelium, through Miiieh the siiupk^ epitlieliuiu beeeiiies stratified i^h, c). 




Fig - riHVrlnDiiiLr H(l(n<u-;nvinoma of tlie hxriso inttwtinc .id, li:vmatoxylin, eosin\ a. 

Mucosa with unciiaiii:'e>l ii-hiihlv; /,. irlaiuls showiiia' caiViiu'iiiatoK- . carcinoiuatous areas iu the 

subniocosa. luu. 



Tlie lat(M' lii^'Towth of tlie epitlielium into the coinieeiive tissue, which 
often (i('eiir> at a very late stage, is a further sigu of uialiguauey — that 
is, of the earcinouiatous transformation of the new-growth.. 




Fig. 326.— Adenocarcinoma of >h<]u:\'-]\ in lo-. i-ss of development (formalin, alcohol, htpmatoxylin, 
eosin). a. Aiueosa ; h, nuiscularis niuct s.i : ( . -uimiucosa : (7. muscularis : f, serosa : /. (/. adenocarcinoma. 
X 15. 

The development of carcinoma from papillary epitheliomata takes 
phiee in the same manner as from the normal skin and mneous mem- 



DEVELOPMENT OF CARCINOMA. 



457 



braiies; and is characterized especially by the infiltration of the epithe- 
lium ii]to the basemeut-tissiie upon which the epithelioma rests. 




Fig. 328.— Tubular adenoma of mamma showing- a beginning transition to carcinoma (formalin, hsema- 
toxylin). a, Branching gland-tubules with simple epithelium; the pericanalicular connective tissue Is 
proliferating and very cellular ; b, c, gland-tubules, the epithelium of which is partly simple, partly strati- 



458 



TUMORS. 



The development of carcinoma from transplanted or misplaced 
epithelium or from remains of foetal structures proceeds in the same 
manner as that of carcinomata arising in either surface or glandular 
epithelium. 

Carcinomatous proliferations of chorionic or placental villi may arise 
either from the foetal ectodermal epithelium of the chorion and its villi, or 
from the cells known as the syncytium which are situated upon the former, 
or from both. They grow from the point of attachment of the villi into 
the neighboring uterine tissue, particularly into the blood-vessels of the 
uterus (Fig. 329, d, d^, e, f, h); and may through the formation of 
thrombi lead to extensive destruction of the tissues of the uterus, and 
may give rise to metastases. Myxomatous degeneration of the chorion 




Fig. 329.— Carcinoma placentare of the uterus (compare von Kahlden. loc. cit.). a, Museularis of the 
uterus; h, large venous blood-spaces; c, thrombus: <h-> intravascular proliferations of the epithelium 
of the chorionic villi into a large blood-space, opened from the uterine cavity, and containing thrombi ; 
these proliferations are either free id) or lie in part upon the vessel-wall ((?]); e, proliferating cell-masses, 
which have forced their way into a smaller vessel ; /, collections of proliferating chorionic epithelium 
within the veins of the uterine musculature; g, thrombus ; /), proliferating cells in the vein-wall. X 70. 

or placental villi (hydatid mole) appears to favor the development of 
such carcinomatous growths. These proliferations may be approi)riately 
designated placentcd and chorionic carcinomata. They have been frec[uently 
described under the names of malignant pJacentoma, deciduoma, chorioepi- 
theJioma, malignant placental polyp, etc. 

Adenomata aud carcinomata cannot always be sharply differentiated from eacli 
other, for tlie reason that tubidar adenomata, especially of tlie intestine, more rarely of 
the thyroid or liver, although possessing a simple cylindrical epitlielium, may grow by 
infiltration, break into the surrounding tissues, and produce metastases. If an especial 
name is to be applied to such growths to distinguish them from the ordinary carciuoma 
adenomatosum or adenocarcinoma, the designation adenoma destruens or malignum 
or carcinomatosum may be used. Further, it should be noted that benign adenomata, 
which have existed as such for a long time, may pass over into carcinomata. 

Carcinomata arising in the skin or mucous membranes are often called cancroids, 
a term used to distinguisli them from other carcinomata, the origin of which was 
formerl}^ thought to be from connective tissue. 

To a certain extent the character of the parent tissue is preserved in cancer cells, 
but a careful examination shows in all cases that there is a certain amount of change 
both in their morphological and in their j^hysiological character {anaphisia). This is 
shown in changes in the form and structure of the cells, their changed behavior toward 



GENESIS OF CARCINOMA. 



459 



stains, in an altered position and arrangement of the cells, and in their changed rela- 
tions toward the surrounding tissues. 

The traumatic displacement of surface-epithelium in wounds may lead to the forma- 
tion of the so-called traumatic epithelial cysts — that is, cysts varying in size from 
that of a hemp-seed to that of a nut, which are lined with epithelium, and, in case they 
arise from the epidermis, contain a pultaceous mass of desquamated epithelium. They 
occur most frequently after puncture -wounds of the volar surface of the fingers and 
in the hollow of the hand. 

Literature. 

(Genesis of Carcinoma,) 
Alberts: Das Carcinom, Jena, 1887. 

Bandler: Chorioepithelioma. Amer. Journ. of Obst., 1902. 
Bayha: Lupuscarcinom. Beitr. v. Bruns, iii., 1888. 

Beneke: Neuere Arb. z. Lelire v. Carcinom (1886-89). Schmidt's Jahrb., 234, 1892. 

Bozzi: Zungencarciuom nach Psoriasis. Beitr. v. Bruns, xxii., 1899. 

Bucher: Beitr. z. Lehre v. Carcinom. Beitr. v. Ziegler, xiv., 1893. 

Cullen : Cancer of the Uterus, New York, 1900. 

Fabre-Domerg-ue : Les cancers epitheliaux, Paris, 1888. 

Fiessinger: La pathologenie du cancer. Rev. de med., 1893. 

Flemming': Ueber Bau u. Entsteliung der Driisen. Arch. f. Anat. u. Phys., 1888. 
Franker. Vom Epithel d. Chorionzotten ausgeh. Carcinom. Arch. f. Gyn., 48 Bd. ; 

Blasenmolen. lb., 49 Bd., 1895; Chorionepitheliom. Encvklop. Jahrb. v. Eulen- 

burg, ix., 1900. 

Franke: Carcin. entart. Epidermoid des Daumens. Virch. Arch., 121 Bd., 1890. 
Friedlander: Ueber Epitlielwucherung u. Krebs, 1877. 

Gaylord: Malignant Growths of the Chorionic Epithelium. Amer. Journ. of Obst., 
1898. 

Hansemann: Ueber asymmetrische Zelltheiluug in Epithelkrebsen. Virch. Arch., 
119 Bd., 1889; Die mikroskop. Diagnose bosartiger Geschwiilste, Berlin, 1897. 

Hauser: Das Cylinderepithelcarcinom des Magens u. des Dickdarms, Jena, 1890; His- 
togenese d. Krebses. Virch. Arch., 138 Bd., 1894, 141 Bd., 1895; Polyposis in- 
testinalis adenomatosa. Deut. Arch. f. klin. Med., 55 Bd., 1895; Histogenese des 
Plattenepithelkrebses. Beitr. v. Ziegler, xxii., 1897; Neue Arb. iiber d. Carcinom. 
Cbl. f. allg. Path., ix., 1898. 

Heidemann: Bedeut. d. kleinzelligen Infiltration in Carcinomen. Virch. Arch., 129 
Bd., 1892. 

Israel: Ueber die ersten Aiifange des Magenkrebses. Berl. klin. Woch., 1890. 
Jung: Zur Lehre vom Carcinom. Langenbeck's Arch., 51 Bd., 1895. 
V. Kahlden: Destruirende Placentarpolypen. Cbl. f. allg. Path., ii., 1891. 
Karg: Ueber das CarciDom. Zeitschr. f. Chir., 34 Bd., 1892. 

Klebs: Ueber das Wesen u. die Erkennung der Carcinombildung. Deut. med. Woch., 
1890. 

Kdster: Die Entwickeluug der Carcinome, Wurzburg, 1869. 

Lubarsch: Primarer Krebs des Ueums (Carcin. cylindromatosum). Virch. Arch., 
Ill Bd., 1888. 

Marchand: Deciduale Geschwiilste. Monatssclir. f. Gebh., 1895. 
Noeg-g-erath : Beitr. z. Structur u. Entwickeluug des Carcinoms, Wiesbaden, 1892. 
V. Notthaift: Eutstehung d. Carcinome. Deut. Arch. f. klin. Med., 54 Bd., 1895. 
Perez: Branchiogenes Carcinom. Beitr. v. Bruns, 23 Bd., 1899. 

Ribbert: Histogenese des Carcinoms. Virch. Arch., 135 Bd., 1894, 141 Bd., 1895; Cbl. 
f. allg. Path., v., 1894; Das pathologische Wachsthum, Bonn, 1896; Die Eutste- 
hung d. Geschwiilste. Deut. med. Woch., 1895. 

Schimmelbusch : Ueber multiples Auftreten primarer Carcinome. Langenbeck's 
Arch., 49 Bd. 

Scliniidt, M. B. : Plexiformes Epitheliom der Haut mit hyaliner Degeneration. Beitr. 

V. Ziegler, viii., 1890. 
Schuchardt; Beitrage zur Entsteliung der Carcinome, Leipzig, 1885. 
Sehiitz : Mikroskopische Carcinombef unde, Frankfurt, 1890. 

Schwalbe: Carcinom in einer tuberkulosen Caverne. Virch. Arch., 149 Bd., 1897. 

Snow: A Treatise on Cancers and the Cancer Process, London, 1893. 

Strobe: Histogenese u. Aetiologie d. Carcinoms. Cbl. f. allg. Path., ii., 1891 (Lit.); 

Cellulare Vorgange in Geschwiilsten. Beitr. v. Ziegler, xi., 1891. 
Tauffer: Carcinom. Degeneration von Dermoidcysten. Virch. Arch., 142 Bd., 1895. 
Thiersch r Der Epithelkrebs, namentl. der auss. Haut, 1865. 

Tillmanns: Ae-tiologie u. Histogenese d. Carcinoms. Langenbeck's Arch., 1., 1895. 



460 



TUMORS. 



Virchow. Ziir Diagnose u. Prognose des Carcinoms. Vircli. Arch., Ill Bd., 1888. 
Waldeyer: Die Entwickelung der Carcinome. Vircli. Arcli., 41 and 55 Bd. ; Saniml. 

klin. Vortr. v. Volkmann, No. 33. 
Williams: Chorioepitlielioma. Amer. Journ. of Obst., 1898 (Lit.). 
Yamagiva; (Jarcin. Degen. von Dermoidcysten d. Ovariums. Vircli. Arcli., 147 Bd., 

1897. 

Zahn: Beitr. z. Histogenese der Carcinome. Vircli. Arch., 117 Bd., 1889. 
ISee also § 124. 

{Traumatic Epitlielial Cysts.) 

Bohn: Traumatisclie Epithelcysten. Virch. Arch., 144 Bd., 1897. 
Garre: Traumat. Epithelcysten d. Finger. Beitr. y. Bruns, xi., 1894, 
Kaufmann: Enkatarrhaphie y. Epithel. Virch. Arch., 97 Bd., 1884. 
Worz: Traumat. Epithelcysten. Beitr. y. Bruns, xviii., 1897 (Lit.). 

§ 124. The structure of a carcinoma is determined by its origin. 
The manner in which the epithelium proliferates and the associated pro- 




Fig. a30.— Horny cancer of the tongue (Miiller's fluid, hgematoxylin, eosin). a, Epithelial plugs with 
epithelial pearls ; b, stroma, X 100. 



liferation of the connective tissue inake it possible to distinguish a con= 
nective=tissue stroma which contains the blood-vessels, and nests and 

strands of cells — the so-called cancer= 
plugs — which lie embedded in the 
stroma. If the cancer grows into a 
tissue having a special structure, the 
stroma may contain muscle-fibres, 
bone trabecul^e, unchanged glandular 
tissue, etc. ; but these I tissues usually 
die after a time. In general a car- 
cinoma possesses an alveolar struc= 
ture, at times suggesting an imi^erfect- 
ly developed acinous gland, at other 
times a tubular gland, so that it is 
possible to distinguisli acinous and 
tubular types of carcinoma. When the 

FIG, 331.-Epitheliaj^plug f rom^ a carcinoma ecll-plugS are SOlid, without a lumCU, 




VARIETIES OF CARCINOMA. 



461 



the growth may be called a carcinoma solidum or merely carcinoma. 
The presence of a lumen in the cell-plugs gives to the growth an appear- 




FiG. 333.— Adenocarcinoma recti tubulare (alcohol, alirai-carmine). a, b. Epithelial glancUubules ; 
c, Ci, stroma ; d, collections of leucocytes in the giand-tubules. X 65. 

ance resembling anatomically the adenomata, and warrants the desig- 
nation carcinoma adenomatosum or adenocarcinoma (Figs. 325-327). 
According to the character of the epithelial cells and" of the cell- 




FiG. 333,— Adenocarcinoma fundi uteri, a, Stroma; /), cancer-plugs; c, isolated cancer-cells. X 150. 

groups formed by them, as well as the nature of the secondary changes 
occurring -in them, there may be distinguished a number of varieties" of 



462 TUMORS. 

carcinomata. Since the character of the cells is clepeudeut upon the 
parent-tissue, certain types of carcinoma are characteristic for certain 
regions of the body, and appear almost exclusively in these parts. 




Fig. 33-i.— Carcinoma simplex mammae (alcohol, hfematoxylin). o. Stroma; 7), cancer-plugs ; c, isolated 
cancer-cells ; c?, blood-vessels ; e, small-celled inflltration of the stroma. X 200. 



(1) Squamous=cened cancers develop in the skin and in those mu= 
ecus membranes covered with squamous cells. They occur, therefore, 
in the external skin, mouth cavity, pharynx, oesophagus, larynx, ^'aginal 
portion of the cervix, vagina, and external genitals. In rare cases they 




Fig. 335.— Acinous carcinoma of the mammary gland with large nests of cells (Miiller's 
fluid, ha?matoxylin). X 100. 



may develop in mucous membranes possessing cylindrical epithelium — 
for example, in the trachea — or in the remains of foetal structures — for 
example, in the remains of the branchial clefts, and in dermoids ; finally 
also in the ependyma of the cerebral ventricles. 



VARIETIES OF CARCINOMA. 



463 



Tlie flat-celled cancer is characterized chiefly by the formation of 
relatively large cell-nests (Figs. 330, a; 331) of irregular shape; but 
they often form also small strands of cells, particularly in the case of 
spreading cancers of the mucous membranes. The epithelial cells which 
are collected in masses show clearly the character of stratified squamous 
epithelium, but on account of their multiplication within the tissue - 
spaces are M^\m\\y xwlymorphous (Fig. 331), and no longer manifest their 
typical characteristics. Very often the formation of keratohyalin and 
cornification takes place within the large epithelial plugs which have 
penetrated into the deeper tissues. The cells which have undergone a 
horny change become arranged in concentric laniinge resembling those of 
an onion (Figs. 323, e; 330, a ; 331). Such cell-nests are known as epi- 
thelial pearls or liorny bodies, and give occasioirfor the designation of the 
tumor as a hotmy cancer. 

Ordinarily the cell=plugs of a squamous- celled cancer are solid, but 
not infrequently gland=like epithelial proliferations are formed, in 




Fig. 336.— Tubular scirrhous cancer of the mammary gland (Muller's fluid, hjematoxylin). a. Spot at 
which there are well-developed oblong nests of cells ; t>, portion of tumor in which the cell-nests have for 
the greater part disappeared. X 100. 

which a central lumen and an epithelial wall may be distinguished, the 
former usually containing necrotic cells and masses of detritus. Ac- 
cording to Krompecher this hai^pens especially when in the develop- 
ment of the cancer the epithelial proliferation is limited to the columnar 
cell -layer of the rete Mali:)ighii. 

(2) Cylindrical=celled carcinomata develop chiefly in those mucous 
membranes possessing cylindrical epithelium — intestines, stomach, respi- 
ratory tract, body of the uterus, and gall-bladder, but occur also in 
glands — ovary, mammary gland, liver, etc. — as well as in the cerebral 
ventricles. Such tumors exhibit, at least in the early stages of develop- 
ment, the character of carcinoma adenomatosum or adenocarcinoma 
(Figs. 325, 326, 332, 333); and also form epithelial structures which 
resemble glands and consist of variously -formed gland -tubules lined by 
a simple or stratified epithelium. A more active proliferation of the 
epithelial cells leads finally to the formation of compact cell-nests pos- 
sessing no lumen (Fig. 333). 



TUMORS. 



The stroma of cylindrical-ci^lled carciiioinata is usually poorly de- 
veloped; and the tumor coiiseciiiciitl y beais the character of a soft can- 
cer, a carcinoma medullare. Xe\ ertheless the cancerous tissue may in 
some cases possess a firm consistence, 

(3) The carcinoma simplex or carcinonia in the narrower sense — that 
is, a cancer whose especial characteristics are derived from the forjn and 
position of the cancer-cells, in that these are arranged simply in irregu- 
lar, compact heaps (carcinoma solidum) — occurs most fi^^quently in 
glands, but may develop also in the mucous membranes and skin. The 
cell -nests are in part very irregularly shaped (Fig. 334), in part round 
(Fig. 335), or in other cases elongated or fusiform (Fig. 336). These 
variations have given occasion to the emj)loyment of the terms carcino= 




Fig. 337.— Section tlirough a segment of a carcinoma of the breast (alcohol, hieiuatoxylin). a. Nipple ; 
Z), tissue of gland; c, sliin : 0. gland-niu t-; : e. carcinomatous masses occupying the place of the gland 
tissue; f, carcinomatous inflltration of fa: tissue; ry, portion of skin iuHltrated with carcinoma; h, nests 
of cancer-cells in the nipple; (, normal gland-lobule; /v, small-celled intiltratioa of the connective tissue. 
Magnified by hand-lens. 

ma acinosum (Fig. 335) and carcinoma tubuiare (Fig. 336) as distin- 
guishing types of corresponding character. It should be noted, however, 
that these different types may be present in the vSame tumor (Fig. 337, 
e, f, g), since the character of the cell-nests dei^ends partly upon their 
manner of growth and partly upon that of the connective -tissue stroma 
in which they develop. At the seat of origin of the tumor the cell-nests 
may have a variety of shaj^es (e) ; in adipose tissue they are rounded 
(/) ; in the unyielding connective tissue of the skin they are small and 
fusiform {g). 

An abundant development of cell-nests within a delicate connective- 
tissue stroma leads to the formation of a carcinoma medullare. A 
marked development of the connective-tissue stroma with the formation 
of relatively few cancer-cells gives rise to a hard tumor, which is called 
a carcinoma durum or a scirrhus (Fig. 336). 



VARIETIES OF CARCINOMA. 



465 



The hard variety of cancer owes its origin to the fact that the cell- 
nests are from the beginning relatively few and small, while the connec- 



^4' 



5 




-'V '.J 



Fig. 338.— Mucoid carcinoma of the mammary sland (Miiller's fluid, hfem-itoxylin, eosin). a, NormTl 
gland tissue: h,c, early stages of carcinomatous proliferation with beginning formation of mucus ; d, 
larger cell-nests with masses of mucus ; e, /, carcinoma tissue showing marlied mucous degeneration. X eO. 

tive-tissne stroma is abundant and hard. Such tumors are formed espe- 
cially when the epithelial proliferation infiltrates into hard connective 




Fig. 339.— Early stages of developuient of a mucoid carcinoma of stomach, arising in an atrophic 
mucosa (formalin, alcohol, haematoxylin, eosin). a, mucosa; h, muscularis mucosge; c, submucosa ; ti, 
muscularis ; c, serosa ; /, g, Mucoid cancer. X 9. 



tissue, as, for example, in the mammary gland and skin, but the same 
characteristics may be exhibited in the case of newly-formed connective 



466 



TUMORS. 




tissue. In the course of time a cancer becomes harder by reason of the 
destruction of a large portion or of all of the nests of epithelial cells (Fig. 
8;^6, //), Avhile the connective tissue increases In amount. An originally 

soft cancer may be= 
come hard through a 
more or less pro- 
nounced shrinkage of 
the cancerous tissue 
in association with the 
induration of the tis= 
sue. Carcinomata of 
the mammary gland, 
stomach, and intestine 
very often show such 
secondary hardening, 
and in cancer tissue 
which has undergone 
such a fibrous change 
the nests of cancer-cells 
may be entirely absent. 
(4) Cancers characterized by peculiar secondary changes arise 
through the formation of especial jjroducts by the cancer cells, or through 
peculiar metamorphoses of the same, or more rarely through changes in 
the stroma. 

Mucoid or gelatinous cancer— carcinoma mucosum {C. gelatinosum, 
G. colJoides) — is that form of carcinoma in which the epithelial cells pro- 
duce mucus (mucin or pseudomucin) or a more colloid-like gelatinous 
substance. Such production of mucus occurs jjarticularly in cancers of 
the intestine, stomach (Fig. 339), and mammary gland (Fig. 338) ; and 
may be manifest in the earliest 
stages of the development of the 
tumor (Figs. 338, b, c; 339,/,^), 
so that the mucoid products of the 
cells collect first in the centre of 
the cell -nests after the manner of 
a gland secretion. Later the 



Fig. 340.— Carcinoma mucosum mammae (alcohol, haematoxylin). 
0, Stroma ; 7), cancer-plugs ; c, alveoli without cancer-cells ; d, cells 
containing spherules of mucus. X 200. 



border of cells surrounding the 
mucoid material is broken 
through, the cells pushed aside, 
separated from the underlying 
structures, and crowded toward 
the centre of the mucus -contain- 
ing alveolus (Fig. 338, d, e, f). 
Ultimately, the epithelial cells 
are wholly destroyed. 

In intestinal cancers the for- 
mation of mucin takes place in 
goblet-cells, which are similar to 
thie goblet-cells occurring under 
normal conditions. In cancer of 
the breast the mucus appears in 

the form of droplets within the cancer-cells (Fig. 340, d), and becomes 
free either by escaping from the cell, or through the complete destruc- 
tion of the cell itself. 




Fig. 341.— Carcinoma with hyaline drops within 
the cell-nests (Carcinoma cylindromatosum ) . a. Cell- 
nest without ; 7>, cell-nest with a few hyaline spher- 
ules; c, cells which have been reduced to strands ar- 
ranged in a network, as the result of the formation 
of numerous hyaline spherules. X 150. 



VARIETIES OF CARCINOMA. 467 

Through the development of mucoid or colloid-like masses within the 
cancer-cell nests, the latter may become studded with hyaline drops, and 
thereby acquire a mesh-like appearance (Fig. 341). Such formations 
were formerly designated as 
cylindromata, and classified 
with the corresponding sar- 
comata. Should it be thought 
desirable to retain this no- 
menclature, such a tumor may 
be designated carcinoma cylin- 
dromatosum ; but it seems un- 
necessary to separate these 
growths from the mucoid and 
colloid carcinomata. 

When the cancer- cells at- 
tain an extraordinarily large 
size, as occurs, for example, 
in flat-celled cancers or in 
cancers of the breast, the tu- 
mor may be termed a carci= 
noma gigantocellulare. If the enlargement of the cells is not due to 
an increase in the amount of i)rotoplasm, but to a swollen condition of 
the cells or to a collection of drops of fluid in the cells and their nuclei 
(Fig. 342), the cells are designsited physalides (carcinoma physaliferum). 

Myxomatous degeneration of the connective -tissue stroma may occur in 
portions of a cancer, so that the cancer-cells become separated from each 
other by myxomatous tissue (Fig. 343). Such growths may be called 
carcinoma myxomatosum. 

Hyaline degeneration of the connective tissue occurs in different 
forms of cancer, but is usually confined to small areas of the tumor. 




Fig. 343.— Carcinoma myxomatodes ventriculi (Mtiller's fluid, hasmatoxylln). a. Cancer-plugs; 5, 
connective-tissue stroma ; c, stroma of myxomatous tissue ; d, cancer-cells which have undergone mucous 
degeneration. X 300. 

Deposits of lime=salts in carcinomata occur chiefly as concretion-like 
masses, similar to those found in psammomata. The concretions may 
form either from the cells or in the connective tissue. They are observed 




Fig. 343.— Enlarged hydropic cancer-cells, from a car- 
cinoma of the mamma (Miiller's fluid, Bismarck- brov^rn). 
a. Ordinary cancer-cells ; hydropic cells containing drops 
of fluid ; c, swollen nucleus ; d, swollen nucleolus ; e, 
wandering cells. X 300. 



468 



TUMORS. 



particularly in papillary adenomata and carcinomata of the ovary, and 
in cancers of the mammary gland. There also occur more exteusive cal- 
cifications, which may lead to complete petrifaction ; and tumors show- 
ing such changes occur chiefly in the skin and subcutaneous tissues, in 




Fig. 344.— Adenosarcoma malignum of the kidney, from a child seven years of age (formalin, hcematoxylin, 
eosin) . a, Tissue with gland-tubules ; b, sarcoma-like tissue, x 300. 

the form of sharply defined, hard, rounded nodules. Some of these 
tumors, according to the descriptions given, are to be classed with the 
carcinomata, others represent calcified atheromata or adenomata of the 
sebaceous glands. 

If, at the same time with development of the epithelial new-growth, 
there occurs a marked proliferation of the connective tissue, leading to 
the formation of a very cellular tissue, there arise tumors which, accord- 
ing to their structure, may be designated adenosarcoma or sarcocarcino= 
ma. Typical examples of this form of tumor occur in the kidneys (Fig. 
344, a, b), forming medullary tumors, the origin of which is probably to 
be referred to a disturbance of development of the kidney. Such tumors 
may show a varying structure in different parts, at one time more of an 
adenomatous or carcinomatous character, at another time ouly a sarco- 
matous. The metastases of such tumors exhibit a similar character. 

Literature. 

{Anatomy of Carcinoma.) 

Becher: Riesenzellenbildung in Kankroiden. Virch. Arch., 156 Bd., 1899. 
Beneke: Carcinom. Bibl. d. med. Wiss. v. Drasche, Wien, 1900. 
Birch-Hirschfeld : Embryonales Adenosarkom der Niere. Beitr. v. Ziegler, xxiv., 
1898. 

Ernst: Verhornender Plattenepitlielkrebs des Bronchus. Beitr. v. Ziegler, xx., 1896. 
Friedlander : Geschwiilste mit hyaliner Degeneration. Virch. Arch., 67 Bd., 1876. 
Glaeser: Untersuch. liber d. Cholesteatom. Virch. Arch., 122 Bd., 1890. 
Goldmann: Verbreitungswege bosartiger Geschwiilste. Beitr. v. Bruns, xviii., 1897. 
Hansemann: Stellung d. Adenoma malignum. Virch. Arch., 161 Bd., 1900. 
V. Kosinski: Schieimmetamorphose der Krebszellen. Cbl. f. allg. Path., iii., 1892. 



CYSTOCARCINOMA. 



469 



Koster: Kankroid mit hyaliner Degeneration. Vircli. Arch., 40 Bd., 1867. 
Krompeclier : Der driisenartige Oberflacbenepithelkrebs. Beitr. v. Ziegler, xxviii., 
1900. 

Xiang-e: Der Gallertkrebs der Brustdriise. Beitr. v. Bruns, xvi., 1896. 
Linser: Verkalkte Epitheliome. Beitr. v. Bruns, xxvi., 1900. 

Iiohmer: Wachsthum d. Haiit- u. Schleirahautcarcinome. Beitr. v. Ziegler, xxviii., 
1900. 

Malherbe: L'epitheliome calcifie. Arch, de "phys., 1881; Rech. s. I'epithel. calcific, 
Paris, 1882. 

H^eug-ebauer : Psammoses Carcinom der Brustdruse. Arch. f. klin. Chir., 48 Bd., 
1894. 

V. Noorden: Das verkalkte Epitheliom. Beitr. v. Bruns, iii., 1888. 
Olivier: Cancer du sein avec corps calcaires. Beitr. v. Ziegler, xvii., 1895. 
Selberg-; Das maligne Adenom. Virch. Arch., 160 Bd., 1900. 
Stieda: Das verkalkte Epitheliom. Beitr. v. Bruns, xv., 1896 (Lit.). 
Wilms: Mischgeschwulste der Niere, Leipzig, 1899. 
See also §§ 123 and 125. 

§ 125. The cystocarcinomata represent a form of tumor which 
stands in the same relation to cancer as the cystadenomata do to the ade- 
nomata. The majority of cancers form no demonstrable secretion, but 
there occur certain varieties, particularly in the group of adenocarcino- 
mata, in which the epithelial cells produce mucus or colloid (thyroid) ; 
and in adenocarcinomata of the liver a secretion of bile has been observed 
(Schmidt). In cystocarcinomata the mucous secretion of the epithelium 
may lead to the formation of large spaces filled with fluid. Cystocarci- 
nomata occur chiefly in the ovary and mammary gland, usually bearing 
the character of a cystocarcinoma papilliferum (Fig. 345), in that the 
cyst-spaces, in certain j)arts or throughout, are either partially (5, c) or 
wholly (d, e) filled with papillary proliferations. These excrescences 




Fig. 345.— Cystocarcinoma papilliferum mammee. a, Stroma ; smooth-walled cysts ; c, cysts con- 
taining papillary proliferations ; c7, evsts entirely filled with papillary proliferations ; e, small, encysted 
papillary growths ; /, adenomatous proliferations ; ty, papilla of the mamma. Reduced about one-third. 

possess a soft, medullary appearance, and when developed in great num- 
bers give to the entire tumor a marrow-like character. 

Both the cyst-wall and the papillary proliferations, which branch in 
the same manner as do those of the papillary cystadenomata, are covered 
with a thick, stratified layer of epithelium (Fig. 346, h, c, d; 347, c). 



470 



TUMORS. 



The papilliB are iisnalh^ slender (Fig. 346, c, d), but througli myxomatous 
degeneration of tlieir connective tissue may attain a large size (Fig. 347, 

























c ■, 









Fig. 346— Cvstocarcinoiua papilliferum ovarii (Miiller's fluid. bEematoxylin). a. Stroma ; epithelium : 

c. (?. papilla?. X 72. 



h). Through total myjcomatous der/eneration of the connective tissue of the 
papillae the latter may ultimately become converted into mucous cysts sur- 
rounded by epithelium. If at the same time the epithelial layers of 




Fig. 347.— Papillary cystocarcinoma of the mamma with papillae which have undergone myxomatous 
degeneration (Miiller's tluid, htematoxylin, eosin). a, Dense connective tissue; h, myxomatous papill* : 
c, proliferatinpr epithelium, arransced in several layers, x 73. 



neighboring x>apill8e become confluent, the epithelium finally comes to 
represent a stroma which incloses balls of mucus. 



INFILTRATION AND METASTASIS. 



The metastases of cyslocai cinomata may liave the character of cauli- 
flower-like, papillary giowths, and this is particularly the case wheu 
ovarian tumors of tliis nature spread throughout the peritoneal cavity. 
Other metastases show the characteristics of ordinary carciuomata. 

Literature. 

{Cijs:tocarcinoma.) 

Baumg-arten : Ovarialkystom mit Metastasen. Vircli. Arch., 97 Bd., 1884. 
Billroth: llandb. d. Frauenkrankheiten, ii., Stuttgart, 1886. 

Leser: Zur pathol. Anat. d. Gesdiwiilste der Brustdriisen. Beitr. v. Ziegler, ii., 1888. 
Pfannenstiel : Papillare Geschwiilste des Eierstocks. Arch. f. Gyn., 48 Bd., 1895. 
Sasse: Cystische Tumoren d. 3Ianima. Langenbcck's Arcli., 54 Bd., 1897. 
Schmidt: Secretioiisvorgange in Krebsen. Virch. Aich., 148 Bd., 1897 (Lit.). 
Stratz: Die Geschwulste des Eierstocks, Beiliu, 1894. 
See also § 123. 

§ I'iG. Growth by infiltration and the involvement of the surround= 
ing tissues takes place, during the early stages of development (Sec. 123), 
through the penetration of the epithelial elements alone into the neigh- 
boring tissue ; but it also happens that in the growth of a tumor into 
neighboring oi'gaiis, the connective-tissue stroma (Fig. 348, d) surround- 




b 




Fig. 348.— Colloid-containing cancer of thyroid infiltrating the thyroid cartilage (alcohol, haeinatoxylin, 
eosin). a. Cartilage; b, cancer-tissue ; c, colloid ; d, cancer-tissue growing into the cartilage. X 85. 

ing the cell-nests breaks into the neighboring tissue (a) and replaces it. 
Such a mode of intiltration occurs to the most marked degree in the case 
of carcinomatous infiltration of cartilage (a) and bones. 

The formation of metastases, w^hich takes place more frequently in 
the case of carcinoma than anj^ other form of tumor, is the natural result 
of its infiltrati\'e mode of growth. In the process of infiltration the 



472 



TUMORS. 



cancer-cells hreali into the Jymph-vessels (Fig. 235), and througli these are 
carried to the lymph-glands. In both i^laces there results a multiplica- 
tion of the transported cancer-cells (Figs. 235 ; 349, d) . In the lymph- 
glands the lymphadenoid tissue becomes replaced by cancer tissue ; the 
lymphocytes vanish, while the connective tissue of the lymph-gland 
serves as a framework for the cancer. 

The development of cancer in the lymph-channels is either limited to 
the filling and distention of the lymph-vessels by the cancer-cells ( Fig. 
235) or it may likewise lead to the formation in this situation of daugh- 
ter-nodules. 

The epithelial obstruction of the Ij^mph-vessels is often very exten- 
sive ; and through the blocking-up of individual lymph -channels or of 
the thoracic duct itself, a retrograde metastasis of cancer-ceJJs may be caused. 
For example, in the case of a cancer of the stomach the lymph-vessels of 
the mesentery or of the lungs, or even of the upper extremities, may be- 
come the seat of metastatic growths. 

The epithelial proliferation breaks into blood-vessels not less frequently 
than into the lymphatics ; and the invasion of the veins by cancer -cells 
is to be regarded as a constant phenomenon. In consequence the vessel- 
lumen becomes filled with cancer- cells, and at a later stage the affected 
portion of the vessel becomes converted into cancer -tissue, the frame- 
work of which is formed through the proliferation of the constituents of 
the more or less altered vessel-wall. The transportation of cancer-cells 




Fig. 349.— Section from an enlarged axillary gland, with beginning development of cancer (alcohol, 
haematoxylin) . a, Germ-centre of a lymph-node ; b, lymph-sinuses ; c, artery ; d, nests of cancer-cells. 
X 60. 

which have been set free in the blood-stream leads to the formation of 
metastases (Figs. 236, b ; 350 ; 351). Here also the cancer growth pro- 
ceeds primarily from the transported epithelial cells; later a stroma for 
the cancer-nodule is furnished by the vessel-walls (Fig. 351) and the ad- 
jacent structures. 



TERATOID TUMORS AND CYSTS. 473 

The daughter -nodules grow partly by expansion and partly by an 
appositional growth through the infiltration of the neighboring blood- 
vessels and lymph -spaces. 

In general the cancer-metastases retain a nodular form. In the serous 
membranes and in the skin diffuse proliferations of tissue may occur, 




Fig. 350. Fig. 351. 



Fig. 350. —Metastatic collection of young cancer-cells within a liver-capillary, arising from a primary 
adenocarcinoma of the stomach (alcohol, hsematoxylin). x 3(X). 

Fig. 351.— Metastatic development of cancer within the liver-capillaries, arising from a primary carci- 
noma of the pancreas (alcohol, carmine) . Both connective tissue and nests of carcinoma cells, have de- 
veloped within the capillaries. X 250. 

leading to dense thickenings which inclose only small cancer-nodules. 
Likewise, the bone-marrow of entire bones or groups of bones may pre- 
sent a diffuse carcinomatosis, in which process there is formed in the 
place of the bone a cancer -tissue, the stroma of which not infrequently 
contains newly-formed osteoid tissue. 

Portions of living cancer-tissue when transplanted from one animal 
to another of the same species may continue to grow and form daughter- 
nodules, in the same manner as in the formation of metastases in the 
individual originally affected. 

Literature. 

(Metastasis of Cancer. ) 

Cuneo: De I'envahiss. du sj'st. lymph, dans le cancer de I'estomac, Paris, 1900. 
Ely: A Study of Metastat. Carcinoma of the Stomach. Am. Journ. of the Med. Sc., 
1890. 

Goldmann: Verbreitimgswege bosartiger Geschwlilste. Beitr. v. Bruus, xviii., 1897. 
Gussenbauer: v. Langenbeck's Arch., 14 Bd., 1872. 

Hanau: Erfolgreiche Uebertragung von Carcinom. Fortschr. d. Med., vii., 1889. 
Stiles: Dissem. of Cancer of the Breast. Brit. Med. Jonrn., i., 1899. 
Wehr: Carciuomimpfungen von Himd 7ai Hund. Langenbeck's Arch. , 89 Bd.. 1889. 
Zehnder: Ueber Krebsentwickelung in Lymphdrlisen. Virch. Arch., 119 Bd., 1890. 
See also § 102. 

3. The Teratoid Tumors and Cysts. 

§ 127. Under the head of teratoid tumors and cysts may be grouped 
those tumor-like formations which are characterized by the fact that the 



474 



TUMORS. 



tissue -formations of wliieli tliej' are composed either do not occur nor- 
mally' at the site in question {heterotopous r/rouih), or at least do not nor- 
mally appear there at the time at whicli tliey ai'e found (Jicfeivchronous 
growth). Part of the teratoid tumors and cysts, which are classed as 
teratomata in the narrower sense, exhibit, moreover, the peculiarity that 
they are comjyosed of a variety of tissues. 

The teratoid tumors and cysts may be conveniently divided, accord- 
ing to their structure and their origin, into tliree groups, as follows: 

(1) The simple teratoid tumors; 

(2) the simple teratoid cysts ; (3) 
the complex teratomata, which in 
part contain tissues derived from 
all tJie germ-layers. In the last- 
mentioned class there may 
further be distinguished certain 
forms which occur particularly 
in the sexual glands. 

The heterotopous t i s s u e = 
growths, which ai'e classed with 
the teratoid tumors, may occur 
in the most various organs, but 
are more frequently found in 
certain regions than in others. 
Among the more common tu- 
mors of this class are the chon- 
dromata and chondroniyxomata 
of the salivaiy glands and the 
testicle, osteomata of the mus- 
cles, lipomata of the pia mater, 
adenosarcomata of the kidney 
containing striped muscle, and 
the adrenal tumors found in the 
kidney. Among those occurring 
more rarely are the chondromata 
and osteomata of the skin or of 
the mammary gland, rhabdo- 
myomata of tlie testicle, etc. 

The occurrence of tissue -for- 
mations in regions in which such 
tissues are not noi-mally present 
can be explained in part l)y the 
assumption that cells or groups 
of cells of a tissue have not un- 
dergone a normal differentiation into definite tissue-forms, but retain 
the capacity of forming different kinds of tissues. IS^evertheless, in 
manj^ cases the explanation is to be sought rather in a germinal aber= 
ration or a misplacement of tissue, in that either in earh^ embiyouic 
life embryonal cells of one organ find their way into the anlage of an- 
other organ, or that later, tissues in process of development or already 
formed are displaced from their normal position. The first process can 
be inferred only from the subsequent aiDpearance of pathological tissue- 
formations; the latter, on the other hand, may at times be recognized, 
later on, iu the anatomical relations. Thus, for example, in the retro- 
grade changes occurring in hernias of the sacral portion of the spinal 




Fig. 352.— Spina bifida occulta with myolipoma inside 
of the spinal canal. (Sagittal section about 1 cm. to 
the left of the median line. Reduced about one-half. 
Taken from von Recklinghausen.) a, Abnormally hairy 
skin ; b, fibrous covering forming the dorsal wall of the 
sacral canal, with a slit-like opening at c ; cZ, spinal 
cord ; e, conus medullaris, lying in the second sacral 
vertebra (2) instead of in the second lumbar vertebra; 
/, Cauda equina: g, dura mater; //, h^, recurrent left 
anterior nerve-roots of the third and fourth lumbar 
nerves ; t, fat tissue ; /<•, strands of muscle ; IT', fourth 
lumbar vertebra; T'', fifth lumbar vertebra; 1-4, sacral 
vertebras. 



TERATOID TUMORS AND CYSTS. 



475 



cord adipose tissue (Fig. 352, i) and muscle -tissue (A) may find their way 
into the spinal canal and the arachnoideal sac and grow around the 
nerves. Arnold observed transposition of fat-tissue, gland-tissue, carti- 
lage and neuroglia at the lower end of the trunk, in a case of myelocyst 
with complete absence of the lumbar, sacral, and coccygeal portions of 
the spinal column. He also found in a lipomatous teratoma of the 
frontal legion that the intracranial portion of the tumor communicated 
with the extracranial through a defect in the cranium. 

Tlie teratoid cysts may be divided into two great groups: the ecto- 
dermal on the one hand, and the entodermal and mesodermal epithelial cysts 
on the other. 

The ectodermal cysts vary m size from that of a pea to that of a 
man's fist. Their walls present ectodermal characteristics, either in that 
they consist only of a smooth connective-tissue membrane, covered with 
stratified squamous cells — the so-called epidermoids ; or the cyst walls 
may present all the characteristics of skin — that is, contain papillae, seba- 
ceous glands, hair follicles, hairs and sweat-glands, and often also subcu- 
taneous fat — the so-called dermoids or dermoid cysts or dermatocysts. 

The cyst-contents consist either of desquamated horny cells alone, or 
of such cells, fat, and blond hair. 

Epidermoids and dermoids are found chiefly in the sMn and subcuta- 
neous tissues, where they present themselves in the form of tumors contain- 
ing a pultaceous material, which r e&emh\e atheromata, i.e., tumors caused 
by the retention of secretion in the excretory ducts of the sebaceous 
glands and in the hair-follicles. Thej^ are also found at the sides of the 
neclc and in the median line either above or below the hyoid bone ; 
further, in the thoracic cavity, particularly in the mediastinum, in thQ peri- 
toneal cavity {v2irQ\j), pelvic cellular tissue, coccygeal region, and in the raj;/i^ 
of the perinewn. Finally, they also appear ivithin the cranium, in the dura 
or in the hypophysis. Of frequent occurrence are the intracranial forma- 
tions which are known as cliolesteatoma or as pearl tumors. These 
growths vary in size from that of a pea to that of an apple ; they form 
spherical or nodular tumors, having a white satiny surface, and consist 
for the chief part of thin, non-nucleated, scale-like cells, arranged in 
closely crowded lamina?. They are invariably situated at some point on 
the pia (Bostrom), and at such places the vascular pia is covered with 
stratified squamous cells, which in the course of years produce the deli- 
cate epithelial scales of which the tumor is composed. The neighboring 
brain tissue and the arachnoid, which may in part extend over the growth, 
are not concerned in the formation of the horny scales. In rare cases 
cholesteatomata may contain sebaceous material and fine hairs in addition 
to the horny scales and cholesterin. In these cases there may be found 
seated here and there upon the pia dermal structures, i.e., true skin tissue 
containing sebaceous glands and hair -follicles, from which the sebaceous 
material and hairs found in the growth arise. The simple cholesteato- 
mata may therefore be designated as epidermoids (Bostrom), those 
containing hair as dermoids. Cholesteatomata occur at the base of the 
brain, in the neighborhood of the olfactory lobe, tuber cinereum, corpus 
callosum, choroid plexus, pons, medulla oblongata (very rarely in the 
spinal cord), and in the cerebellum. 

The dermoids and epidermoids under consideration doubtless owe 
their origin to a transplantation of epithelial germs to the sites in 
question. In the case of the epidermoids probably only embryonal epi- 
thelial cells are transplanted ; in dermoids embryonal dermal tissue is 



476 



TUMORS. 



also transplaDted. The intracranial cholesteatomata originated proba- 
bly iu an early implantation of epidermal anlage in the pia. Mediasti- 
nal dermoids probably depend upon disturbances of development of the 
thymus, which arises from the ectoderm. The dermoids on the sides of 
the neck arise from remains of the branchial cleftS;, particularly of the 




Fiu. ;i5:j. Adenoma-like isolation in tbe submucosa of a portion of the mucous membrane of the small 
intestine, giving rise to a ridge-like prominence of the mucosa 3 cm. in length (alcohol, haematoxylin). 
From a child six weeks of age. a, h, c. Normal intestinal wall ; d, e, portions of mucosa included within 
the submucosa ; /, mucous tissue rich in cells. X 35. 

second; those hanging from the hyoid bone or lying beneath it are prob- 
ably to be regarded as the remains of the ductus thyreoglossus. Dermoids 
of the pelvic cellular tissue may be explained as arising from epithelial 
inshoots from the perineum. 

Biniple entodermal and mesodermal epithelial cysts are charact^er- 
ized by a lining of cylindrical cells, which are of ten ciliated. They occur 
most frequently in the broad ligament and tubes. They are found also 
in other portions of the peritoneal cavity, jn the intestine, in the neigh- 
borhood of the trachea and bronchi, in the lungs, pleura, neck, tongue, 
glandular organs, etc. They form cysts varying in size from that of a 
pin-head to that of a man's head. 

The occurrence of these cysts may be explained in most cases by the 
persistence of foetal glands or canals or by the separation through 
constriction of portions of entodermal or mesodermal epithelial tubes. 
In the neck remains of the internal branchial clefts, in the posterior por- 
tions of the tongue the remains of the ductus thyreoglossus or of epithe- 
lial buds and glands developing from the same (Schmidt), in the oesoph- 
agus and respiratory tract snared -off portions of the intestinal canal or 
of the air-passages, or remains of the communication between alimen- 
tary tract and air-passages, may form the foundation for the develop- 
ment of such cysts. In the broad ligament, uterus wall, and tubes the 
cysts arise from remains of the canals of the Wolffian body and the duct 



TERATOID TUMORS AND CYSTS. 



4T7 



of Gartner; in the cervix, portio vaginalis, vagina, and hymen they 
arise frojn the remains of the latter ; in the peritoneal cavity in part from 
snared-off portions of the intestine (^enterocysts) , or in part from portions 
of the iirachus {urachus-cysts). Within the glands — for example, the 
liver or the kidneys — portions of the gland-tubules may become con- 
stricted off during the period of development, and later develop into 
cysts (adenocysts). 

Cysts located in the central nervous system or its immediate neigh- 
borhood — for example, at the lower end of the trunk — may arise from 
the medullary canal (myelocysts). 

The origin of the cysts lined with cylindrical epithelium can usually 
be determined only from their position and the character of their walls, 
but in the majority of cases the origin can usually be ascertained beyond 
doubt. The diagnosis can be made with the greatest certainty when the 
misplacement of the separated portion is slight (Fig. 353, d, e), and when 
the formation still shows clearly the character of the mother-tissue. 

The significance of ectodermal, entodermal, and mesodermal cysts is 
dependent upon their position, size, and the secondary changes which 
occur in them. Their size varies from that of a pin-head to that of a 
man's head. Among the secondcu^y changes — aside from inflammatioii — 
may be mentioned the development of adenomata and carcinomata. For 
example, remains of the Wolffian body which are present in the dorsal 
wall of the uterus near the angles of the tubes (von Eecklinghausen), or 




Fig. 354.— Adenoma-like remains of the Wolffian body, within the uterine musculature (formalin, alcohol, 
haematoxylin, eosin) . a, Muscle tissue ; b, glandular tissue ; c, sections of vessels. X 100. 

in the broad ligament in the inguinal region (Aschoff, Pick) may give 
rise to adenomata, cystadenomata (Fig. 354, b), or adenomyomata. Der- 
moids may be the seat of development of a squammis-ceUed cancer (branchio- 
genicand subcutaneous carcinoma); while from separated portions of the 
intestinal mucous membrane (Fig. 353) it is probable that cylindrical- 



478 



TUMORS. 



celled carcinomata may take their origin. Ci/sts, cystadpnomata, and car- 
cinomata may develop in the jaw from misx)laced portions of the epUhelial 
aniage of the teeth. 

Literature. 

{Ectodermal, Entodeniud, and Mesodermal Teratoid Cysts, Tissue -transplan- 
tations, and Misplacements.) 

Albrecht: Nebenmilzen. Beitr. v. Ziegler, xx., 1896. 

Arnold: Hygroma colli con genitiim. Yircli. Arch., 33 Bd., 1865; Angeb. lipomaloser 
Teratom der Stirn. lb., 43 Bd., 1868; Congenitales zusammeiigesetztes Lipoin der 
Zimge und des Pharyux mit Perforation in die Scliadelhohle. lb., 50 Bd., 1870; 
Behaarte Polypen der Rachenmimdhohle. lb., Ill Bd., 1888; Ein Knorpelhaltiges 
angeborenes Fibrom des Scheitelsmit Hypertrichosis. Beitr. v. Ziegler, viii., 1890; 
Myelocyste, Transposition von Gewebskeimen w. Sympodie. lb., xvi., 1894. 

Ascholf: Cysten, Ergebn. d. allg. Path., ii., 1897 (Lit.); Cystisches Adcnotibrom d. 
Leistengegend. Monatsschr. f. Gebh., ix,, 1899. 

Askanazy. jlie bosartigen Geschwiilste der in der Niere eingesclilossenen Neben- 
uierenkeime. Beitr. v. Ziegler, xiv., 1893. 

Bostrom: Piale Epidermoide, Dermoide ii. Lipome ii. diirale Dermoide. Cbl. f. allg. 
Path., 1897 (Lit.). 

Beneke: Ziir Lehre v. d. Versprengung von Nebennierenkeimen in den Nieren nebst, 
Bemerkungen zur allg. Onkologie. Beitr. v. Ziegler, x., 1891. 

Brunner: Spina bifida mit Hypertrichosis. Yirch. Arch., 129 Bd., 1892. 

Bruns, P. : Branchiogene Carcinome. Mittheil. a. d. chir. Klinik zu Tubingen, i. 
1884. 

Buttersack: Congen. Knorpelreste am Halse. Virch. Arch., 106 Bd., 1886. 

Chiari: Genese d. Atheromcysten. Cbl. f. allg. Path., 1890; Zeitschr. f. Heilk., xii., 

1891. 

Cohnheim: Allgemeiue Pathologie, i., Berlin, 1882. 

Cullen: Adenomyoma of the Round Ligament. Johns Hopkins Hosp. Bull., 1892. 
Dehler: Atheromcysten am Halse. Beitr. v. Burns, xx., 1898. 

Deichert: Knorpel u. Knochen in d. Tonsilleu (Reste d. 2 Keimenbogens). Yirch. 
Arch., 141 Bd., 1895. 

Demoulin; De quelques productions heterotopiques a epithelium prismatique cilie, 
Paris, 1866. 

Doderlein: Embrj^on. Driisengeschwulst d. Kierengegend. Cbl. f. Krankh, d. Har- 
norg.. 1894. 

Dossekker; Urachuscysten. Beitr. v. Bruns, x., 1893. 

Eberth; Flimmerepithelcysten d. Leber u. d. Gehirus. Virch. Arch., 85 Bd., 1866. 
Frank. Cholesteatom d. weichen Hirnhaute. Inaug.-Diss., Marburg, 1897. 
Franke: Das Atherom. Arch. f. klin. Chir., 34 Bd., 1887; Virch. Arch., 121 Bd., 
1890. 

Frobenius: Ueber einige angeb. Cystengeschwiilste des Halses. Beitr. v. Ziegler, 
vi., 1889. 

Goebel; Vom Zahnsystem ausgehende Kiefertumoren. Cbl. f. allg. Path., 1897 (Lit.). 
Grawitz: Ueber die'sog. Lipome der Nieren. Virch. Arch., 93 Bd., 1883. 
Gurlt : Die Cj^stengeschwiilste des Halses, Berlin, 1855. 
Haffter: Ueber Dermoide. Arch. d. Heilk., xvi., 1875. 
Hasse: Die Beziehungen der Morphologic zur Heilkunde, Leipzig, 1880. 
Hektoen : Vitelline-Duct Remains at the Navel. Amer. Journ. of Obst., 1893. 
Helbing: Rhabdomyom an Stelle d. 1. Lunge. Cbl. f . .allg. Path., ix., 1898. 
Hess: L'eber eine subcutane Flimmercyste. Beitr. v. Ziegler, viii., 1890. 
Heusing-er: Hals-Kiemenfisteln mit Knorpelresten. Virch. Arch., 29 Bd., 1864. 
Hildebrand: Unters. liber Spina bifida (Gewebstranspositionen). Deut. Zeitschr. 

f. Chir,, 36 Bd., 1893; Langenbeck's Arch., 46 Bd., 1893; Cysten u. Fisteln d. 

Halses. lb., 49 Bd., 1894; Spina bifida (Gliom in Hydrencephalocele). Deut. 

Zeitschr. f. Chir., 36 Bd., 1893. 
Hueter: Angeb. Darmgcschwulst. Beitr. v. Ziegler, xix., 1895. 

Joachimstlial : Spina bifida occulta mit Hypertrichosis. Virch. Arch.. 131 Bd., 1893. 
Kelly: Hypernephromas of the Kidney. Phil. Med. Journ., 1898. 
Kdster: Hygroma colli cougenitum. Verb. d. Wiirzb. pliys.-med. Ges., iii., 1872. 
Kiihne: Zur'pathol. Histologic d. Cystenbildung. Virch. Arch., 158 Bd., 1900. 
Lannelongue et Achard; Traite des kystes congenitaux, Paris, 1886. 



COMPLEX TERATOMATA. 



479 



Lesag-e ct Legrand: Des neoplasies iierveiises d'origine centrale. Arch, de pliys., 

Malassez: Sur se role des debris epitlieliaux paradentaires. Arch, de phys., 1885. 
Mallory; Sacrococcygeal Dimples, Siuiises, aud Cvsts. Am. Journ. of the Med. Sc., 
1S9-J. 

Marchand: Rliabdomyom der Dammgegend. Virch. Arch., 100 Bd., 1885. 
Mermet Lcs kystes coiigen. dii raphe genito-perineal. Rev. de chir., 1895. 
Meyer: Ueber epitheliale Gebilde im JMvometrium, Berlin, 1899. 
Mintz: Nabeladeuom. Dent. Zeitschr.'f. Chir., 51 Bd., 1899. 
Neumann: 3Iyoma striocellulare d, Hodens. Virch. Arch., 103 Bd., 1886 
Paltauf; Schilddrusentiimoren im Kchlkopf, u. d. Luftrohre. Beitr. v. Ziegler, xi., 
1891. 

Perez: Bianchiogene Carcinome. Beitr. v. Brims, 23 Bd., 1899. 

Permann: Cvstoses Sacrococcygealteratom (grosse Myelocyste). Arch. f. kiln. Chir., 
49 Bd., 1895. 

Pflam: Dermoidcysten des Mediastinums. Zeitschr. f. Heilk., xvii., 1896. 
Phole: Angel). Cysten d. Genitoperinealraphe. Beitr. v. Bruus, xx., 1898. 
Pick Adenomyome d. Leistengegend u. d. !Scheiden2:ewolbes. Arch. f. Gyn., 57 Bd., 
1S99. 

V. Reckling-hausen : Uutersuchuugen liber Spina bifida. Yirch. Arch., 105 Bd., 
1886; Die Adenomyome u. Cystadenome d. Uterus, Berlin, 1896. 

Reinhold: Oelcyste auf d. Schlafeuschuppe. Beitr. v. Brims, yiii., 1892. 

Ribbert Spina bifida occulta. Virch. Arch., 132 Bd., 1893. 

Richard: Geschwlilste der Kiemenspalten. Beiti-. z. klin. Chir., v. Bruns, iii. 

Samter; Ein Beitrag z. Lehre y. d. KeimengangsgeschAviilsten. Virch. Arch., 112 
Bd., 1888. 

Sang-er: Dermoidcysten d. Becken'oindegewebes. Arch, f Gyn., 37 Bd., 1895. 

Schmidt: Ueber die Flimmercysten d. Zungenwurzel, Jena, 1896. 

Schoch: Congen. zahnhaltige Cyste der Unterlippe. Inaug.-Diss , Basel, 1893, 

Schulz: Embryon. Arschniirungen y. Epidermis. Virch. Arch., 95 Bd., 1884. 

Virchow: Die krankhaften Geschwiil^^te. Beil. ak. Monatsber., 1875; Ueber einen 
Fall von Hygroma cysticum glutaeale congeiiitum. Virch. Arch., 102 Bd., 1885. 

Volkmann: Bi'anchiogene Carcinome. Cbl. f. Chir., xxii., 1885. 

Westenryk: Mediastinalcysten. Prag. med. Woch., xxv., 1900. 

Wette: Fistelu u. Cysten d. Sacrococcygealgegend. Langenb. Arch., 47 Bd., 1894. 

Wyss: Ziir Kenntnlss heterologer Flimmercsyten. Virch. Aich., 51 Bd., 1870. 

Zahn: Kiemcngangscysten. Deut. Zeitschr. f. Chir., xxii., 1895; Myxosarkom der 
Wange bei sechsmonatl. Fotus. Deut. Zeitschi. f. Chir., xxii., 1885; Congen. 
Knorpclreste am Halse. Virch. Arch., 115 Bd ; Flinunei'epithelcysten des Oeso- 
phagus d. Leber u. d. Pleura. Viich. Aivli., 143 Bd., 1896 (Lit.). 

Zoppritz: jMultiloculiire Kiemenganoscvsten. Beitr. v. Bruns, xii., 1894. 

See also 128 and 147. 

§ VIS. Teratoid cysts of a complicated structure aiicl solid tera- 
tomata ai'e found, outside of the sexual glands, in the same regious as 
tlie simple teratoid cysts, but show a particular predilection for the region 
of the coccyx. The complex character of the cysts is shown by the pres- 
ence in the cyst-wall of cartilage, bone, fat tissue, mucous glands, smooth 
and strii^ed muscle fibres, ner\'e-tissue, and tissue of a sarcomatous or 
carcinomatous nature. Dermoid cysts may also contain teeth, and further 
also ciliated epithelial cysts. The solid teratomata occur, in the first 
place, as liairy iwlypi (nose, throat, and mouth) — that is, as polyi^oid tu- 
mors covered with hairy skin, and consisting essentially of adipose 
tissue, which may also contain muscle fibres, cartilage, bones, teeth, and 
cysts. Another group consists of ilio^^ Mdney-iumors^ hioh, in addition 
to tubular glands, inclose sarcomatous tissue, cartilage, fibrous tissue, 
adipose tissue, and muscle tissue, in rare cases also ectodermal tissues. 
In the vagina and cervix uteri of childi'en there occur tumors, for the 
greater pait of a racemose character, which, in addition to connective 
tissue, myxomatous tissue, round and spindle-celled tissue, also contain 
smooth and striped muscle-fibres, and in rare cases also cartilage. Fi- 
nally, there occur tumor-like growths of a very complicated structure in 



480 



TUMORS. 



the cranium, thorax, abdomen, neck, lower ja w, and especially in the region 
of the coccyx. They contain the most varied forms of tissne : connective 
tissue, adipose tissue, cartilage, bone, gland tissue, muscle, nerve aud 
brain substance, as well as ectodermal and eutodermal cysts. They may 
further inclose rudimentary, or completely formed, or at least easily 
recognizable, portions of the body. 

Both the complex teratoid cysts and the solid teratomata are in 
many cases to be regarded as local disturbances of development char- 
acterized by a misplacement of tissue or a separation of tissues by 
constriction within a single individual {^monogeminal tissue-implanta- 
tion, autocMJionous teratoma). The hairy polyx3i of the throat, the cystic or 
solid teratomata at the base of the skull or in the hypophysis may be ex- 
plained by the assumption of a misplacement of ectodermal tissue. The 
presence of cartilage and mucous glands in teratoid cysts of the medias- 
tinum may be explained by the proximity of the trachea. The teratoid 
mixed tumors of the kidney may be explained by the assumption that in 
the kidney region, in addition to kidney-tubules and remains of the 
Wolffian body, products of the mesenchyma arising from the myotome 
may undergo proliferation. The occurrence of squanious-celled forma- 
tions in such tumors must depend upon the fact that ectodermal tissue 
has found its way into the kidney anlage. The presence of striped 
muscle-fibres of cartilage in tumors of the vagina and uterus is explaina- 
ble by the assumption of an implantation of myotome or of anlage of the 
vertebrae (sclerotome) ; but many writers hold the opinion that striped 
muscle may be formed from unstriped. Wilms believes that the Wolffian 
duct and its development give occasion to and are the cause of the im- 
plantations into the cervix and vagina. In the case of the teratomata of 
the coccygeal region the manifold character of these growths may be ex- 
plained by the fact that portions of the terminal vertebrae, of the pelvis, 
and of muscular tissue, as well as remains of the neuroenteric canal, 
the hind-gut, and the medullary canal, take part in the formation of the 
tumor. In the intracranial teratomata, as well as in the simple dermoids, 
tissue -implantations probably form the basis for the growth. Moreover, 
there exists indeed the possibility of another mode of origin for these 
growths — namely, the presence of a rudimentary twin, a bigeminal im- 
plantation. Such an assumption is well founded in all those cases in 
which the teratoma contains fully developed or rudimentary parts of the 
body, or tissue-formations which cannot be explained by the assumption 
of a misplacement of the tissue elements of a single foetus at the spot in 
question. Ekehorn regards the complex dermoids of the mediastiuni, 
which contain skin, cartilage, bone, and the constituents of mucous mem- 
branes, as bigeminal implantations. Lexer emphasizes such a mode 
of origin for the teratoid mixed tumors of the abdominal cavity (see g§ 
129, 132, and 147). 

Literature. 

(TJie Complex Teratoid Cysts and Tumors.) 

Arnold; Beliaarte Polypen der Rachen-Mimdholile. Virch. Arch., Ill Bd., 1888. 
Aschoff: Cysten. Ergebn. d. allg. Path., ii., 1897 (Lit.). 
Beck: Teratom d. Hypophysis cerebri, Zeitschr. f. Heilk., 1883. 
Borst: Die angeb. Geschvvi\lste d. Sacrah-egion. Cbl. f. allg. Path., ix., 1898 (Lit.). 
Birch-Hirschfeld : Nierengeschwlilste. Beitr. v. Ziegler, xxiv., 1898. 
Bostrom: Piale Epidermoide, Dermoide u. Lipome u. durale Dermoide. Cbl. f. allg. 
Path., 1897 (Lit.). 



TERATOMATA OF OVARY AND TESTICLE. 



481 



Braun: Die Doppelbildnngen ii. die angeb. Gescliwiilste d Kreuzbeingegend, Leipzig, 
1862. 

Buzzi: Angeb. Gescliwiilste der Sacrococcygealgegend. Virch. Arch., 109 Bd., 1887. 
Christian: Dermoid Cj sts and Teratomata of the Ant. Mediast. Jour, of Med. Res., 
1902. 

Eberth: Intracranielles Teratom. Virch. Arch., 153 Bd., 1898. 
Ekehorn: Dermoidcysten des Mediastinums. Arch f. klin. Chir., 56 Bd., 1898. 
Eng-elken: Embr. Drilsengeschwulst d. Nierengegend. Beitr. v. Ziegler, xxvi., 1899. 
Frank: Tumor sacralis (Teratom m. Dermoid- u. Flimmercysten). Prag. med. Woch., 
1894. 

Flirstenheim • Kiemengangauswiichse m. Knorpel-Gerust. Jahrb. f, Kinderheilk., 
1895. 

Hennig: Congen. Sacraltumoren. Beitr. v. Ziegler, xxviii., 1900. 
Hertzog" and Lewis: Embryonal Renal Adenosarcoma. Amer. Journ. of Med. Sc., 
1900. 

Jastreboff: Angeb. Geschwulste in der Gegend des Kreuzbeins. Virch. Arch., 99 Bd., 
1885. 

Jores: Dermoidcyste mi t Cystosarkom der Lunge. Virch. Arch., 133 Bd., 1893. 
Kirmisson: Chirurg. Krankheiten angeb. Ursprungs, Stuttgart, 1899. 
Kolaczek: Dermoid d. Ovariums mil Bauchfellmetastasen. Virch. Arch., 75 Bd,, 
1879. 

Koslowski: Hodensack-Tcratom. Virch. Arch., 148 Bd., 1897. 

Lexer: Teratoide Geschwiilste d. Bauchhohle. Arch. f. klin. Chir., 61 Bd., 1900; 

Fotale Inclusionen in der Bauchhohle. lb., 62 Bd., 1900. 
Linser: Sacralteratome. Beitr. v. Bruus, xxix., 1901. 
Marchand: Sacraltumoren. Eulenburg's Realencyklop,, xxv., 1899. 
Marwedel : Ein Fall von persistirendem Urmund (Retroanal entwickeltes Darmstilck 

mit sacralem After). Beitr. v. Bruns, xxix., 1901. 
Middeldorpf: Angeb. Geschwiilste in der Gegend des Kreuzbeins. Virch, Arch., 

100 Bd., 1885. 

Montgomery: A Terat. of the Abdom. Cavity. Journ. of Exp. Med., iii., 1898. 

Moussaud: Des inclusions foetales. These de Paris, 1861. 

Nasse: Genese der sacrococcygealen Teratome. Langenb. Arch., 45 Bd., 1893. 

Otto: Ueber einen c(mgenit. behaarten Rachenpolypen. Virch. Arch., 115 Bd., 1889. 

Pommer: Teratologische Mittlieilungen. Cbl. f. allg. Path,, i., 1890. 

Ritsclil- Angeb. Sacralgeschwiilste. Beitr. v. Bruns, viii., 1892. 

E-olleston; Adeno-chondrosarcoma of the Mediastinum. Journ. of Path., iv., 1896. 

Saxer: Teratom im III. Ventrikel. Beitr. v. Ziegler, xx., 1896 (Lit.), 

Schmidt: Bezieh. d. Steissgeschwiilste zu d. Steissdriise. Virch. Arch., 102 Bd., 

1888; Zwei Falle von Geschwulsten in der Gegend des. Schwanzbeines. Arb. a, d. 

chir, Universitatspoliklinik v. B. Schmidt, Leipzig, 1891. 
Siegenbeek van Heukelom Tum. cong. du cou. Rev. de trav. du Lab., Boer- 

haave, 1899, 

Stolpe: Angeb. Geschw. d. Kreuzsteissbeingegend. Deut. Zeitschr. f, Chir., 50 Bd., 
1899, 

Strassmann u. Strecker: Ein Teratom im recliten Seitenventrikel. Virch. Arch., 
108 Bd. 

Sutton: Dermoids or Tumors containing Skin, Hair, Teeth, etc., London, 1889. 
Virchow: Teratoma myomatodes mediastini. Virch. Arch., 53 Bd., 1871. 
Weigert: Teratom d, Zirbeldruse. Virch. Arch., 65 Bd., 1875. 

"Wilms: Dermoidcysten u. Teratome. Deut. Arch. f. klin. Med., 55 Bd., 1895 (Lit,); 
Die Mischgeschwiilste der Niere, Leipzig, 1899 ; der Vagina u. der Cervix, Leipzig, 
1900. 

See also §§ 127 and 147. 

§ 129. The teratomata of the ovary and testicle occur partly in the 
form of dermoid cysts, and partly as solid tumors in which multiple cys- 
tic formations are present. The dermoid cysts are found chiefly in the 
ovary ; the solid tumors in the testicle. 

The so-called dermoid cysts of the ovary form rather thick-walled 
cysts, varying in size from that of a pea to that of a man's head, and are 
filled with a fatty material containing blond hair. At some point in 
the wall there will be found extending into the cyst-cavity a villus-like, 
nodular, flattened, or septum-like prominence^ which is covered with hairs and 



482 



TUMORS. 



often studded with teeth (Fig. 355, b, e, d). The upper layeis of this 
prominence contain the characteristic structures of the skin (Fig. .'356, 
a, a^, a^, b), namely, hair-follicles with hairs, sebaceous glands, and sweat- 
glands; subcutaneous fat is also usually present (/). In the decider 
layers are found other tissue-formations, such as cysts and tubes lined 
with ciliated columnar epithelium (d), bone (g), cartilage, teeth (h), 




Fig. 355.— Portion of the wall of a dermoid cyst of the ovary. Smooth wall; h, prominence consist- 
ing of fat and cutaneous tissues; c, swollen protuberance, bent down upon itself above and bearing hairs 
and teeth id). Natural size. 



muscle-tissue (also heart-muscle [Katsurada] ), brain-tissue (/), nerves, 
groui)s of ganglion-cells, mucous glands, intestinal mucosa, and thyroid 
tissue, as well as pigmented formations resembling the rudimentary tis- 
sues of the eye. Kidney and liver tissues have not yet been found. The 
remaining portion of the cyst-wall of the dermoid is either covered with 
cylindrical epithelium or is bare ; if hairs are present in tliis portion, 
they are the result of a secondary implantation, and may be surrounded 
by granulation-tissue, often also by giant-cells. If in association with 
the cysts containing fat and hairs there are also found cysts filled with a 
serous or mucoid fluid, the latter may be exi)laiued as arising through 
the cystic dilatation of spaces of the dermoid which are lined with cylin- 
drical cells. More frequently, however, they represent formations re- 
sulting from the cystic degeneration of neighboring ovarian follicles or 
of adenomatous new-growths. The ovary may be entirely destroyed by 
the dermoid; but remains of its tissues are often present (A-). In very 
rare cases several dermoids may develop coincidently in one ovary ; a 
double-sided occurrence is seen in about fifteen per cent, of all cases. 



EMBRYOMA. 



488 



Ovarian dermoids are observed most frequently in individuals of middle 
age, but occur also in children. 

The most characteristic feature of ovarian dermoids lies in the fact 
that they contain elements of all three germ-layers, and that a certain law 
in the arrangement of the different elements is observed. The deriva- 
tives of the ectoderm and mesoderm, in particular the skin and its ap- 
pendages, also bone and teeth, and often brain substance, are developed 
to the most marked extent; while entodermai formations, cylindrical- 
celled tubules, and mucous glands are ordinarily developed to a much 
less degree, and lie concealed in the deeper parts of the growth. The 
structure of the growth as a whole gives the impression of a rudimentary 
embryo with an unequal development of ecto- and entodermai tissue, and 




Fig. 356.— Section through a prominence in a mulfilocular dermoid (alcohol, nitric acid, hsematoxylin. 
eosin). a, «], a^^ Epidermis: 1), corium with sebaceous glands; c, sinus lined with squamous epithelium ; 
d, sinus lined with cylindrical epithelium ; e, tubular glands ; /, fat-tissue ; g, bone ; ?i, teeth ; i, brain- 
tissue with corpora amylacea ; fc, ovarian tissue. X 5. 

such tumors have therefore been appropriately designated as embryo- 
mata (Wilms). 

The solid teratomata of the ovary are much more rare than the der- 
moid cysts. They form tumors which are composed of a confused mix- 
ture of the most varied tissue-formations, viz., epidermis, epithelial 



484 



TUMORS. 



pearls, hairs, sebaceous glands, sweat glands, tubules, and cysts lined 
with columnar cells, acinous glands, connective tissue rich in cells, adi- 
pose tissue, muscle, cartilage, and bone. In rare cases teeth, intestine, 
thyroid and brain tissue of a rudimentary character may Ix' i)resent. 

Since these formations also contain elements of all tJircc f/ci-iii-hii/ers, and 
are distinguishable from the dermoids only througli the lack of auy regu- 
lar order of arrangement of the diffei'eiit tissues, and tliroogh the more 
rudimentary development of the individual tissues, the>' miiy likewise be 
classed with the embryomata. With reference to their lack of any 
structural organization approaching that of the human embryo, Wilms 
has designated these formations as embryoid tumors. 

Since the embryoma contains elements of all three germ-layers, in 
part in orderly arrangement, the genesis of such a tumor may be ex- 
plained by the assumption of a development from an ovum. Wilms and 
others believe that the development of an unfertilized ovum may be 
assumed ; but nothing is known concerning parthogenetic development 




Fig. 357.— Cougenital adenocvsloma (teratoma ) of the testicle with pigmentation and formation of car- 
tilage (Miiller's fluid, haematoxylin) . rt. Connective-tissue stroma ; l\ simple cubical epithelium ; c, strati- 
fled cylindrical epithelium; (?. stratiQed ciliated cylindrical epithelium; e, pigmented epithelium lining 
gland-tubule ; h pigmented connective-tissue cells ; (/, cartilage in connective tissue ; /(, cj't tilage lying in a 
gland-tubule. " (Section taken from tumor pictured in Fig. 315.) X 100. 

of the ova of mammals, and the occurrence of such seems very improba- 
ble. Bonnet regards it as much more probable, that either in the devel- 
opment of a fertilized ovum, in the early stages of division, a blastomere 
(or several) may be delayed in division and later give rise to an inde- 
pendent formation containing elements of all germ4ayers, or that a fer- 



TERATOMATA OF TESTICLE. 



485 



tilized polar body (the fertilization of the polar body has been demon- 
strated in vertebrates) finds its way between the blastomeres of a devel- 
oping ovum, and later develops within the embryo. The first assumption 
seems more probable, and the embryomata of the ovary may consequently 
be regarded as rudhneiitary nniovnl finn ))}al formations (see §§ 128 and 



Fig. 358.— Teratoma (adenomyosarcoma) of the testicle (formalin, haematoxyltn, eosin). a. Cellular tissue 
with bands of muscle ; &, gland-tuVtule. X 100. 



147), which are to be placed in the same category with the foetal inclu- 
sions of other organs. The fact that the ovaries (and testicles) form the 
favorite seats of such growths is probably dependent upon the fact that 
the urogenital anlage in its earliest stage forms relatively such a large 
part of the embryonal anlage (Bonnet), or that the blastomeres, from 
which the sexual glands later arise, more easily than others take on an 
especial development, which leads to the formation of a rudimentary 
twin. 

The teratomata of the testicle occur most frequently in forms which 
according to their structure are designated as adenocystoma, chondroade- 
noma, chondrosarcoma, adenom/yosarcoma (Fig. 357), cystosarcoma, cysto- 
^ carcinoma, etc. In some cases the formation of cj^sts with fluid contents 
forms the most striking feature of the tumor (Fig. 315) ; in other cases 
cysts are found onlj in certain parts of the growth; and, finally, in 
still other cases the tumor may be solid throughout. These growths 
may reach the size of a child's head. They may be congenital, but de- 
velop more frequently in adult life, and then grow rapidly. 

The lining of the cysts is, as a rule, of entodermal character, but may 
vary in one and the same cyst (Fig. 357). Simple cubical (Fig. 357, b) 
and cylindrical epithelium either with or without cilia, as well as strati- 
fied ciliated epithelium (d) and pigmented epithelium (e), may be found. 

Ectodermal tissue is present only in scanty amount, and is limited to 
pigmented epithelium or to scattered groups of cells showing cornifica- 
tion; or it maybe eutirely absent, or, at all events, caunot be demon- 



486 



TUMORS. 



strated in the case of tumors of large size. Besides the cysts, mucous 
giands may also be found. 

Of the connective-tissue substances, fibrous tissue, myxomatous tissue, 
cartilage (Fig. 357, g, h), and occasionally also muscle (Fig. 358, a), fat 
tissue, and more rarely bone, are present. 

Teratomata of the character of dermoids, containing, as in the case 
of the ovarian dermoids, such structures as skin, brain tissue, cranial 
and tracheal tissues, and more rarely teeth and structures resembling 
the eyes, are of rare occurrence in the testicles, but are found both in 
children and in adults. 

To what extent the different teratomata of the testicles are to be classed 
with the embryomata, or to what extent they can be explained by the 
assumption of tissue implantations at later stages of embryonal develop- 
ment, cannot at present be determined. When elements of all the germ- 
layers are present in the tumor, the assumption is justified that the 
growth belongs to the embryomata or embryoid tumors, and has arisen 
in the same manner as has been assumed in the case of the ovarian der- 
moids. The presence of single tissue -formations — as, for example, of 
cartilage or of muscle — in tumor-formations of a more simple character, 
may be explained by the assumption that such tissues find their way into 
the anlage of the testicle during the period of embryonal development. 

Numerous hypotheses have been advanced concerning the origin of the terato- 
mata of the sexual glands, particularly of the dermoids. Of the more recent investi- 
gations concerning this question, those of Wilins ai'e in particular worthy of consider- 
ation. This author has carried out extensive researches into the structure of these 
growths, and has emphasized with great force that the fact that these tumors contain 
elements of all germ -layers necessitates the assumption of their development from an 
ovum. Bonnet has thrown light upon the question from the standpoint of the em- 
bryologist, and likewise emphasizes the view that the complex teratomata which con- 
tain elements of all germ-layers must arise from an ovum, but that portions alone of a 
ripe and fertilized ovum, as a fertilized polar body, may develop into such an em- 
bryoma. The attempt of Bandler to refer the embryomata of the germinal organs to 
ectodermal implantations occurring accidentally during the development of the uro- 
genital system cannot be regarded as successful, inasmuch as the anlage of many 
formations contained in embryomata (teeth, thyroid, eje) cannot possibly be located in 
the region of the urogenital anlage. 

Literature. 

( Teratoid Cysts and Tumors of the Sexual Glands. ) 

Arnsperger: Dermoidcyste des Ovariums. Virch. Arch., 156 Bd., 1899. 
Bandler: Die Dermoidcysten des Ovariums, Berlin, 1900; Amer. Journ. of Obstet., 
1901. 

Baumgarten: Dermoidcvsten d. Ovariums m. augenahnlichen Biidungen. Virch. 
Arch., 107 Bd., 1887." 

Bonnet: Giebt es bei Wirbelthieren Parthenogenesis? Ergebn. d. Anat., ix., Wies- 
baden, 1900; Aetiologie d. Embryome. Monatsschr. f. Gebh., 1900. 

Delbet: Pathogenic des tumeures heterotopiques. L'Un. med., 1895. 

Katsurada: Zur Lehre v. d. sog. Dermoidcj^sten d. Eierstocks. Beitr. v. Ziegler, 
XXX., 1901. 

Kockel: Hodenteratom. Chir. Beitr, Festschr, f. B. Schmidt, Leipzig, 1896. 
Kolaczek: Dermoid d. Ovariums m. Bauchfellmetastasen. Virch. Arch., 75 Bd., 
1879. 

Marchand: Teratom des Ovariums. Bresl. arztl. Zeit., 1881. 

Neumann: Dermoid d. Ovariums m. centraler JSTervensubstanz. Virch. Arch., 104 
Bd., 1886. 

Pilliet et Costes: Les epitheliomes du testicule. Rev. de chir., 1895. 

Sabbe: Tumeurs dermoides de I'ovaire. Ann. de la Soc. de med. d. Gand, 1898. 

Scheiber: Solides Ovarialteratom. Virch. Arch., 133 Bd., 1893. 



TERATOMATA OF THE SEXUAL GLANDS. 



487 



Tauflter; Carcinornatose Degen. v. Ovarialcysten. Virch. Arch., 142 'Bd., 1806. 
Waldeyer: Die epithelialeu Eierstocksgeschwiilste. Arch. f. Gyn., i., 1870. 
Wilms- Oermoidcysten u. Teratome. Dent. Arch. f. klin. Med., 55 Bd., 1895 (Lit.); 

Die soliden Teratome d. Ovariums. Beitr. v. Ziegler, xix. ; Die teratoiden Gesch- 

wiilste d. Hodens. lb., xix., 1896 (Lit.); Embryome ii. embryoide Tumoren d. 

Hodens. Deut. Zeit. f. Chir., 49 Bd., 1898; Multiple Embryome d. Ovariums. 

Monatsschr. f. Gebh., 1899. 
Yamagiva: Dermoidcyste d. Ovariums m. krebsiger Degeneration. Yirch. Arch., 147 

Bd., 1897. 
See also 127 and 128. ..... 



CHAPTER IX, 



Disturbances of Development and the Resulting 
Malformations. 

I. General Considerations Regarding Disturbances of Development 
and the Origin of flalformations. 

§ 130. After the copulation of the sexual uuclei has taken place, the 
development of the embryo proceeds by a progressive division of nuclei 
and cells, associated Avith which there arise in an orderly manner especial 
groui3ings of cell -complexes and differentiation of the same into especial 
tissues and organs. The multiplication of the cells, as well as the devel- 
opment of individual cell -groups into especial organs and parts of the 
body, depends uj)on intrinsic causes, and is controlled by the character- 
istics which the embryo has received through the transfer of the inherit- 
able paternal or maternal characteristics at the moment of the union of 
the sexual nuclei, which are to be regarded as the carriers of inheritable 
characteristics. It follows, therefore, that the characteristics of the 
species as well as the especial x)eculiarities of the given individual are in 
general already predetermined in the germ, and the development of the 
embryo proceeds essentially under the control of innate moulding forces. 
^sTevertheless, this development is not accomplished without the influence 
of environment, in that the embryo of necessity receives its nourishment 
from the maternal organism, and at the same time is exposed to mechani- 
cal influences on the part of its membranes and of the uterus. These 
influences may therefore operate to modify the development of the foetus. 

In every species of animal, man included, both the bodily form and 
the configuration of the oi'gans present a particular type, which exi^erience 
has shown constantly to recur, and which is therefore looked upon as 
normal. If more or less marked departures from this type occur, which 
can be referred to a more or less marked abnorinal course of the intra- 
uterine development, the condition is designated as a congenital mal- 
formation. When the departure from the normal structure is very 
marked, so that the affected individual is grossly malformed, it is spoken 
of as a monster. 

According to common usage, the term malformation is usually ap- 
plied onlj^ to anomalies in the form of the body as a whole, or to single 
parts of it which present to external inspection rather striking departures 
from the normal. It is nevertheless entirely correct to use this term for 
pathological conditions of intrauterine origin, which consist not so much 
in an abnormal change in form, but rather in an incomplete or faulty 
organization of the affected part or organ. 

A malformation affecting a single individual is known as a single 
malformation or single monster ; one made up from two individuals is 
termed a double malformation or double monster. 

Malformations may oive their origin to either intrinsic or extrinsic causes. 

488 



CAUSES OF MALFORMATIONS. 



489 



As intrinsic causes may be considered all such as already exist in 
the germ, so that in the development of the embryo malformations may 
arise spontaneously without the aid of extrinsic influences. When such 
Si malformation occurs for the first time in a family, it must be regarded 
as a prima?^ germ-vcuiation. This may be explained in one of two ways: 
either one or both of the sexual nuclei entering into union may have 
been abnormal, or both may have been normal, but from their union a 
variety has arisen which from one point of view is to be regarded as 
pathological (cf. § 18). 
It is also possible that 
disturbances in the j)roc- 
esses of fertilization can 
give rise to pathological 
variations. 

If a similar malfor- 
mation has already oc- 
curred in the parent, the 
case may be regarded as 
one of inheritance. If the 
malformation appearing 
is a peculiarity which 
was not present in the 
parents, but did show 
itself in more remote 
ancestors, while want- 
ing in the intermediate 
links, the phenomenon 
is designated as atavism. 

As primary germ- 
variations appear the 
same malformations 
which are also inherit- 
able — that is, only those 
malformations are in- 
heritable which origi- 
ally appeared as primary 
germ - variations. To 
such inheritable malfor- 
mations belong the in- 
crease in the number of 
the fingers and toes (polydactylism), malformations of the hands and 
feet, abnormal hairiness, harelip, and certain pathological conditions of 
the nervous system, as, for example, multiple fibromata, of the peripheral 
nerves. 

Under extrinsic causes of malformations are to be considered espe- 
cially concussio7i, pressure, disturbances in the supply of oxygen ayid nourish- 
ment, and infections. 

Concussions of the uterus may in all probability directly damage the 
embryo at a very early stage. At a later stage of development the harm- 
ful effects of trauma are probably more often to be sought in a tearing 
loose of the egg and in decidual haemorrhages, whereby the nourishment 
of the embryo is disturbed. It is evident that haemorrhages from other 
causes, also changes in and contaminations of the maternal blood, as 
in infections, and, further, pathological conditions of the uterus itself, 
.27 




Fig. 359.— Malformation of the head, due to adhesions of the mem- 
branes to the frontal region (Arm adherence of placenta to uterus) . 
a, Membranous sac inclosing a vascular, spongy tissue containing 
numerous cysts ; Z), eye ; c, lip ; d, funnel-shaped depression lined 
with mucous membrane; e, left, gj, right ala nasi; /, connective- 
tissue bands. Reduced one-fourth. 



490 



DISTURBANCES OF DEVELOPMENT. 



rise to their characteristic changes in the latter. 





may have a harmful intlueiice upon the developing egg ; yet all these 
conditions pro)3ably lead more often to the death of the foetus and the 
expulsion of the egg than to the development of a malformation. Infec- 
tious diseases of the mother may be transmitted to the foetus and give 

An abnormal pressure 
from the uterus or its mem- 
branes may be exerted upon 
the embryo, especially when 
there is a deficient amount of 
amniotic fluid; and malforma- 
tions of the extremities (Fig. 
362), in particular, not infre- 
quently show evidences of press- 
ure having been exerted. 

From the anatomical findings 
in many malformations it ap- 
pears that pathological condi= 
tions of the amnion may exert 
a damaging influence upon the 
embryo and give rise to different 
forms of malformations. 

This may be brought about 
through abnormal adhesions be- 
tween the embryo and the amnion, 
as well as hj 2))'essi(re of the am- 
nion npon the embryonal anJage. 
Even at the birth of the child 
adhesions in the form of bands 
and threads (Figs. 359,/; 361) 
may not infrequently be dem- 
onstrated, and their connection 
with the malformed parts is 
such as to leave no doubt that they stand in a causal relation to the 
malformation. Such adhesions may give rise to severe malformations 
of the cerebral (Fig. 359) or of the facial (Fig. 360) portions of the 
head, ^^'ot infrequently portions of the extremities are snared off by 
amniotic bands (Fig. 361), and may be completely amputated and then 
absorbed. 

To what extent these adhesions of the amnion with the foetus are to 
be referred to primary adherence and intergrowth, and to what extent 
to inflammatory processes of later occurrence, is yet a disputed question. 
!N'ot infrequently the adhesions at birth are no longer visible and the 
affected part presents only a scar-like appearance (Fig. 360). 

According to Dareste and G-eoffroy St. -Hilaire, an abnormal tightness 
of the amnion may easily exert a harmful influence upon the embryo. 
An abnormal closeness of the cephalic cap of the amnion may cause the 
malformations known as anencephalia, exencephalia, cyclopia, and cebo 
cephalia or arrhincephalia (§ 135) ; while an abnormal tightness of 
the caudal cap may give rise to sirenomelia (§ 139). Further, the cleft 
malformations of the anterior abdominal and thoracic walls (§ 137) are 
also associated with a faulty development of the amnion ; still the latter 
condition is often not so much the cause as it is a concomitant of the 
malformation, which may be the result of a variety of causes, and, in- 
deed, is often to be regarded as a spontaneous or primary malformation. 



Fig. 360.— Malformation of the face, caused by amni- 
otic adhesion and pressure. Asymmetry of the f ace, o. 
Malformed nose; rudimentary lid-clefts; c, Ci, 

clefts in the upper lip and alveolar process of the upper 
jaw ; d, intermaxillary bone with prominent lip ; e, 
oblique facial fissure closed by scar tissue so as to form 
a groove. 



CAUSES OF MALFORMATIONS. 



491 



The period at which the iiijui ioiis intlneuce is active varies greatly, 
and consequently so does the extent of the damage done by it. The 
earlier the damage occurs, the greater the extent of the injury. Mal- 
formations in the narrower sense of the term arise chiefly during the first 
three months, during the period when the body and its individual parts 
are devel oiling their proper forms. Damage to the foetus at a later 
period occasions changcH irhirh are more closely allied to those acquired after 
birth. 

Some malformations are typical — that is, they always appear in the 
same form; while others again are wholly atypical, so that the most 
astonishing anomalies of form may arise. The latter are for the greater 
part the result of extrinsic harmful influences ojDerating secondarily, 
while the former may be regarded as owing their origin chiefly to in- 
trinsic causes, although external influences may also cause ty]3ical mal- 
formations. 

Geoffroy St.-IIilairc ("Hist. gen. ct partic. des anomalies cle I'organization chez 
riiomme et les animaiix," Paris, 1832-37) discards entirely the teaching of a primary 
abnormality of the germ {ILdler and ^yinslolr), and attributes arrests of development 
purely to mechanical influences. Panura Uutersuch. liber die Entstehung der Miss- 
bildungen," Berlin, 1860) agrees with him on the whole, although he admits the possi- 
bility of a primary abnormality. He produced malformations in hens' eggs by means 
of temperature variations and by varnishing the shells. Dareste ('' Recherches sur la 



Fig. 361.— Hand stunted by amniotic adhesions ; ring-finger snared off ; middle and index fingers grown 
together and distorted. Reduced one-sixth. 

Fig. 362.— Hand stunted and deformed by pressure ; thumb absent ; hand flattened ; great bending 
and shortening of the forearm. Reduced one-fifth. 

production artiticielle des monstruosites," Paris, 1877) made similar experiments and 
produced malformations due to arrested development by keeping the eggs in a vertical 
position, by varnishing the shells, b}' raising the temperature above 45° C., and also by 
irregular warming of the eggs. 

Very recently L. Oerlacli, Fol, Wdvynsky, RicJiter, Ron.r, aud Schidtze have in par- 
ticular carried on experiments in this line, and have attempted, Avith partial success, to 




Fig. 361. 



Fig. 362. 



492 



DISTURBANCES OF DEVELOPMENT. 



produce malformations in chicken-embryos through the localized influence of radiant 
heat, variations of tempei-ature, varnishing the eggs, changes of position, injuries, 
removal of a portion of the white of the egg, and by agitation. Rovx, experimenting 
on frogs' eggs, found that, after destruction of one of the tirst segmentation-spheres, 
tlie other continued to develop and formed the half of an embryo, thus demonstrating 
that each of the first two segmentation-cells, corresponding in their position to the right 
and left body-halves, contams within itself the anlage material for the corresponding 
half of the body. But since the body-half which is wanting may later be replaced by 
subsequent development from the undestroyed half, and a whole structure be produced, 
each half must also possess the power of producing also the other half. According to 
investigations by HerUtzka, Driesch, Morgan, Wilson, and others, the first two or even 
the first four segmentation-cells in tritons. teleosts, ascidians, and echinoderms possess 
the power of forming an entire embryo. 

Scliultze experimented on the eggs of amphibia; these normally always assume 
such a position that the darkly pigmented protoplasmic substance of lighter specific 
gravity lies above, the heavier clear protoplasm rich in yolk granules lies below. By 
placing the eggs in an abnormal position and preventing their return to the normal 
position malformations may be produced, the degree of malformation standing in direct 
relation to the size of the angle formed by the line of gravity and the abnormally- 
placed axis of the egg. By turning the egg through an angle of 180° in the two-cell 
stage a double monster is regularly produced. The same turning in the eight-cell 
stage causes a complete cessation of development. These disturbances arise from dis- 
placements consequent upon the sinking of the heavier and a rising of the lighter con- 
stituents of the egg. 

According to investigations by 0. Hertwig, the eggs of axolotl, when kept in a 0.7- 
per-cent. solution of sodium chloride, undergo a pathological development, which is 
confined to the central nervous system in the region of the head and trunk. The so- 
dium-chloride solution acts only upon those portions of the ectoderm which are in the 
process of changing into ganglion-cells; and as a result, with otherwise normal devel- 
opment, portions of the central nervous system may be lost. 



Literature. 

{Malformations and Their Origin. ) 

Ahlfeld: Berichte und Arbeitenaus der geburtshiilfl. Klinik zu Marburg, 1885-86 ; Die 

Missbildungen des Menschen, Leipzig, 1880, 1882. 
Ballantyne: The Diseases and Deformities of the Foetus, i. and ii., Edinb., 1893, 1895. 
Barfurth: Leber organbildende Keimbezirke u. kiinstliche Missbildungen d. Amphi- 

bieneies. Anat. Hefte, Wiesbaden, 1893. 
Braun, C. : Neue Beitr. z. Lehre v. d. amniotischen Bandern, Wien, 1862. 
Charrin et Gley : L'influence teratogSne des prod, microbiens. Arch, de phys., 1896. 
Davaine: Monstre, Monstruosite. Dictionn. encyclop., abgedr. in L'oeuvre de Da- 

vaine, Paris, 1889. 

Dareste: Rech. sur la production artif. des monstruosites, ii. ed., Paris, 1894. 
Delage: Structure du protoplasma et les theories de I'heredite, Paris, 1895. 
Driesch: Entwickelungsmechan. Studien. Zeitschr. f. wiss. Zool., 53, 55 Bd., 1891, 

1892; Anat. Anz., vii., 1892. 
Duval: Teratogenic. Path. gen. publ. p. Bouchard, i., Paris, 1895. 
Endres: Entwickelungsmechanik. Eulenburg's Jahrb., vii., 1897. 
Endres u. Walter: Anstichversuche an Eiern von Rana. Arch. f. Entwickelungs- 

mech., ii., 1895. 

Fol et Warynsky : Rech. exp. sur la cause de quelques monstruosites. Recueil zool. 

Suisse, i., 1883. 
Forster : Die Missbildungen des Menschen, Jena, 1865. 

Gerlach: Production v. Zwergbildungen im Hiihnerei. Biol. Cbl., ii., 1883; Neue 
Methoden auf dem Gebiete der experimentellen Embryologie. lb. , vii. , 1889 ; Anat. 
Anz., 1887. 

Giaccomini: Anomalies de developp. de I'embryon humain. Arch. ital. de biol., ix,, 
1888; xviii. and xix., 1892; xx., 1893; xxiv., 1895; Influence de I'air rarefie. lb., 
xxii., 1894. 

Guinard: Precis de teratologic, Paris, 1893. 

Gurlt: Literatur iiber Missgeburten. Virch. Arch., 74 Bd., 1878. 

Hertwig: Exper. Erzeug. thier. Missbildungen. Festschr. f. Gegenbaur, Leipzig, 

1896; Mechanik und Biologic, Jena, 1897. 
Hirst and PiersoL- Human Monstrosities, Philadelphia, 1891. 



SINGLE MONSTERS. 



493 



His: Ueber mechanisclie Grundvorgange tliierischer Formbildung. Arch. f. Anat., 
1894. 

Israel: Angeb. Spalten d. Olirlappchens, ein. Beitr. z. Vererbungslehre. Virch. 

Arch., 119 Bd., 1891. 
Kirmisson: Chh'. Krankheiten angeb. Ursprungs, Stuttgart, 1899. 
Kollmann: Die Korperform menschl. normaler u. pathol. Embryonen. Arch. f. An., 

1889. 

Klistner: Ueber eine noch nicht bekannte Entwickeluugsursache amputirender 
amniotischer Faden. Zeitschr. f. Geb., xx., 1891; Die Pathologic des Fotus, 
Stuttgart, 1888. 

LannGlongue et Menard: Affections congenitales. I. Tete et cou, Paris, 1891. 
Marchand, : Missbildungen. Eulenburg's Realencyklop., xv., 1897 (Lit.). 
Mitrophanow : Teratogenet. Studien. Arch. f. Entwiclvelungsmech. , i., 1895. 
Morian: Die schrage Gesichtsspalte. Arch. f. klin. Chir. , 1887. 
Moser: Missbild. durch amniotische Bander. Prag. med. Woch., 1894. 
Otto : Monstrorum sexcentorum descriptio anatomica, 1844. 

Panum: Zur Kenntniss d. physiol. Bedeutung d. angeb. Missbildungen. Virch. 

Arch., 72 Bd., 1878. 
Piersol: Teratology. Ref. Handbook of Med. Sc=, 2d ed., 1903. 

Richter: Ueber die experimentelle Darstellung der Spina bifida. Anat. Anz., iii., 
1888. 

Jloux: Zur Entwickelungsmechanik des Embryo. Zeitschr. f. Biol., xxi., 1886; 
Kiinstliche Hervorbringuug halber Embr3^onen durch Entfernung einer der beiden 
ersten Furchungskugeln, u. Wachsthumsentwickelung der fehlenden Korperhalfte. 
Virch. Arch., 114 Bd., 1888; Die Entwickelungsmechanik der Organismen, AVien, 
1890; Ueb. das entwickelungsmechanische Vermogen jeder der beiden ersten 
Furchungszellen des Eies. Verb. d. Anat. Ges., vi., 1892; Ueber die Specification 
der Furchungszellen und liber die bei der Postgeneration und Regeneration 
anzunehmenden Vorgitnge. Biol. Cbl., xiii., 1893; Die Methoden zur Erzeugung 
halber Froschembryonen. Anat. Anz., ix., 1894; Einleitung zum Arcliiv fiir 
Entwickelunsgmechanik der Organismen. Arch. f. Entwickelungsmeclianik, i., 
1894. 

Schultze: Die Bedeutung der Sclnverkraft fiir die organische Gestaltuug, sowie liber 
die rait Hlilfe der Schwerkraft mogiiclie klinstliclie Erzeugung von Doppelmiss- 
bildungen. Verb. d. Phys.-med. Ges., 28 Bd., 1894; Entwickelungsgeschichte, 
Leipzig, 1896. 

Taruffi: Storia della teratologia, i.-viii., Bologna, 1881-96; Sull' ordiuamento della 

teratologia. R. Accad. delle Sc. dell' 1st. di Bologna, 1896, 1898. 
Virchow: Descendenz u. Pathologic. Virch. Arch., 103 Bd., 1886. 
Wiedersheim : Der Bau des Menschen, Fieiburg, 1893. 

Ziegler: Konnen erworbene patholog. Eigenschaften vererbt wcrden u. wie entstehen 
erbliche Krankheiten u. Missbildungen. Beitr. z. pathol. Anat., i., 1886; Die 
neuesten Arb. liber Vererbung u. Abstammungslehre, u. ihre Bedeutung fiir die 
Pathologic. lb., iv., 1889. 

For literature of Malformations, see Anat. Anz., i.-xix., 1886-1901; and Cbl. f. 
allg. Path., i.-xii., 1890-1901. 

§ 131. Single malformations may be conveniently divided into five 
gronps, according to the kind of change which characterizes them. 

As arrests of development or monsters due to defective develop- 
ment (monstra per defectum) may be classed in the first place all those 
malformations in which the whole or a part of the body is abnormally 
small and imperfectly developed (liypoplasia) , and also those malfor- 
mations characterized by the coniplete absence or very great stunting 
{agenesia or ajylasia) of individual organs or parts of the body. In this 
class belong, for example, the absence of the brain or of parts of it, or 
abnormal smallness of the brain, defects in the septa of the heart, defects 
and stunting of the extremities, etc. 

If, in the case of parts or organs of the body which are normally 
formed by the union of anlage which are originally separated, such 
union should fail to take place as the result of a primary or secondary 
disturbance of growth, the arrest of development may show itself in the 
form of clefts and reduplications. Thus, for example, imperfect develop- 



4:U 



DISTURBAXCES OF DEVELOPMENT. 



ment of the plates fonniiiL:,' the anterior Ih)(1\ - wall <;ives rise to clefts in 
the median line of the thorax and abdonuMi : a failnre of union of the 
jnaxillary processes of the tirst branchial arch with each other or with 
the nasal process of the frontal bone gi\ es rise to clefts in the face. 
Defective union of the bilateral portions of the female genital tract 
results in a more or less extensive reduplication of the uterus or vagina. 

AYhen the anlage of two organs lie near to each other, these may 
under certain conditions become united so as to produce a coalescence or 
adhesion between two organs or parts which should normally be sepa- 
rated. For example, the kidneys at times may be more or less united, 
and the eyes may be more or less completely merged into a single organ. 

nalformations due to excessive growth (monstra per excessum) 
are characterized in iravt hy abnojinal size of individual x^ints, and in part 
by an increase in Jiuniher of the same. For example, an extremity or a 
portion of one, as a finger, may reach an abnormal size {2)((rfl((I e/iant 
growth), or the whole body may be involved in the abnormal growth 
(general giant growth). An increase in number occurs ^particularly in the 
case of the mammary gland, spleen, adrenals, and lingers. Additional 
glandular organs are designated aceesso)'i/ or supernunierary o)-gans. 

As malformations due to an abnormal disposition of organs (mon- 
stra per fabricam alienam) are designated by Forster certain anomalies 
of the internal organs of the thorax and abdomen, which are character- 
ized by an abnormal position of the organs, and in part also by changes 
in the relation of individual parts to each other. In this class belongs 
the condition known as situs transrersus— that is, the transposition of the 
thoracic or abdominal organs, or of both. Further, various defects in 
the heart and great vessels inay also be classed here, though it should be. 
noted that these are more properly regarded as arrests of devdopment. 

A fourth group of nmlformations includes those characterized by 
displacement of tissues and by the persistence of foetal formations, as 
already mentioned in §^ 127 and 128. 

Finally, as a hfth group may be classed those malformations ex- 
hibiting a mixture of the sexual characteristics, known as true and 
hermaphroditism. True hermaphrodites possess both male and female 
sexual glands; false hernmphrodites are unisexual, but the remainder 
of the sexual apparatus does not correspond to the sexual gland, or there 
is a simultaneous formation of organs belonging to both the nuile and 
female. A part of these malformations are arrests of development ; 
others are to be regarded as cases in which from the original bisexual 
anlage the oi'gans of both sexes have developed, whereas normally the 
anlage of one sex undergo a retrograde change instead of developing, 
and persist only in a rudimentary form, 

^ 132, Double monsters (monstra duplica^ are malformations in 
which the entire body or a part of it is duplicated. The twins are al- 
ways of the same sex, and are usually united at corresponding portions 
of the body. The dux:)licated parts are sometimes equally, sometimes 
unecpially developed ; in the latter case one of the parts is dwarfed and 
appears as a parasitic appendage to the well-developed individual or 
is inclosed within the body of the latter, AVe may accordingly distin- 
guish equal and unequal forms of double monsters. 

All douhle monsters a)-ise frou) a single egg a^ul derehp from a single 
germinal vesicle. The disturbance of development may occur during 
the course of the segmentation process, but is lirst recognizable when 
from the germinal vesicle there is formed a double eml)rgo)ial anlage. A 



DOUBLE MONSTERS. 



495 



double monster may then arise either through the two embryonic areas 
being united from the very beginning, or that, originally sej)arated, 
they infringe upon one another in their growth and blend to a greater or 
less extent. A second i)ossibility is the formation within a single em- 
bryonic area of two primitive streaks and then two medullary grooves, 
which nvdj remain entirely separate from each other or only partially 
blend. A third possibility would be a single primitive streak, but a 
medullary gi oo^ e which is double either in part or in the whole of its 
extent. Finally, it is possible that under certain conditions a duplica- 
tion takes place at a later period of development and then affects oidy 
indi^•idual parts of the axial zone or only the parietal zone. 

The causes of a duplication of the enihryonal anlage in a single germinal vesicle are not 
known. According to Fol, double and multiple monsters arise through the abnormal 
impregnation of an ovum with two, three, or more spermatozoa ; but other observa- 
tions [Born) indicate that ova fertilized by two or more spermatozoa do not develop. 
Accoixling to MarclLand, the doubling of the anlage is to be referred to conditions exist- 
ing before the beginning of segmentation, either to conditions within the egg before fer- 
tilization, or to the fertihzation itself. Wiedemann and Wetzel hold the opinion that the 
origin of double monsters dates from the moment of impregnation, and is due to the 
fertilization of ova containing two germinal vesicles by tw^o spermatozoa. 

Successful experiments in the artificial production of double monsters from the eggs 
of animals have been made in recent j-ears by Geriach, 0. Schultze, and Born. Gerlach 
produced double monsters (anterior duplication) from hens' eggs by varnishing these 
before incubating, leaving free only a Y-shaped spot in the region of the primitive 
streak. Inasmuch as he only rarely succeeded in obtaining such results, it is possible 
that these malformations, which not infrequently occur in chickens, Avere accidental. 
Schultze obtained double monsters b}^ turning frogs' eggs during the two-cell stage 
through an angle of 180° (cf. § 130). Speruiann was able to produce double-headed 
embryos of tritons by constriction of the embryonal anlage before the closure of the 
medullary plate to form the medullarv groove. Born succeeded in uniting together 
portions of the larvae of amphibia, not only of the same kind, but also of diilerent 
species, genera, and families {Rana e-sculertta with Bombinator igneus, and with 
Triton). The conditions were most favorable for union in the case of larvse of about 
3 mm. length. Not only the external coverings of the body, but also the anlage of 
organs (liver, intestine, heart-tube), were blended into a united organ, the union being 
completed through specific tissue of the same kind. From all these experiments the 
conclusion may be drawn that double monsters may be produced from a normal egg 
through secondary influences, and that neighboring embryonal anlage may grow one 
into the other. On the other hand lies the possibility that especial conditions within 
the egg before fertilization may be the cause of the duplication. According to Schultze, 
this may possibly lie in the presence of two nuclei or of two spindles, or in an over-ripe 
condition of the egg with a tendency to fragmentation into tw^o halves, which divide 
shortly before fertilization. Therefore a normally fertilized ovum in the two-cell 
stage may be brought through some influence (as in the experiment of Schultze) to the 
formation of tAvo individuals. 

Literature. 

(Double 3Ionste)'S. ) 
Ahlfeld: Die Missbildungen des Menschen, Leipzig, 1880, 1882. 

Born: Furchungen des Eies bei Doppelbildungen. Breslauer arztliche Zeitschr., 1887; 
Ueber Doppelbildungen beim Frosch. lb., 1882; Ueber Verw^achsungsversuche 
mit Amphibienlarven, Leipzig, 1897, ref. Deut. med. Woch., 1898, S. 126. 

Dareste: Product, des monstruosites. Compt. rend. Ac. des sc., 1861, 1863, 1864, 
1865, 1866. 

Debierre: La theorie de la monstruosite double. Arch, de phys., ii., 1890. 
Debierre et Dutilleul: ]\[onstres doubles du genre synote. Arch, de plu'S.. ii., 1890. 
Fol: Recherches sur la fecondation, etc., 1879. 
Forster : Die Missbildungen des Menschen, Jena, 1865. 

Geoffroy Saint-Hilaire : Hist. gen. et partic. des anomalies de I'organisat. chez 

I'homme et les animaux, Paris, 1832-37. 
Geriach. L. : Ueber die Entstehungsweise der vorderen Verdoppelung. Deut. Arch., 



496 



DISTURBANCES OF DEVELOPMENT. 



f. klin. Med., 42 Bd. ; Die Eutstelnuiixsweise der Doppelniissbildiinfren. Stuttsrart, 
1883. 

Gschier: Thoracopao-iis tetrabrachius aeqiialis. Prag. med. Wocli., 1892. 
Klaussner: Melirfaclibiidimgen bei AVirbeltbiereu, Miinchen, 1890. 
Kormann ; Ueber lebende Doppebnissbilduuo-en der Xeuzeit. Schmidt's Jahrb. , cxliii, 
1869. 

Lochte: Eiu Fall vou Doppelmissbildimgen. Beitr. v. Ziegler, xvi., 1894. 
Marchand; ^lissbildungeu, Eulenbiirg's Realencyklop., xv.. 1897. 
Myschkin: Zwilliusi-sschwaiigerschaft ii. angeb. Missbildiinireu. Yirch. Arch., 108 
Bd.. 1887. 

Panum: Untersuclumgeu liber die Entstehiing der Missbildimgen, Berlin, 1860: Zur 

Kenntniss d. phys. Bedeutuug d. Missbildimgen. Yirch. Arch., 72 Bd., 1878. 
Rauber. Die Theorie der excessiveu Monstra. Virch. Arch., 71, 73, 74 Bd., 1877-78. 
Schafer: Ueber eiuen Dicephalus. Beitr. v. Ziegler, xxvii., 1900. 
Schultze, O. : Ueber die Bedeutiino- der Scliwerkraft. etc. Verb, der plivs.-med. 

Gesellsch., 28 Bd., 1864; Arch. f.^Entwickekmgsmech.. i.. 1894; Entwickelimo- d. 

Doppelbildimgeu. Cbl. f. allg. Path., x.. 1899. 
Sobotta. Xeiie Anschauiiugen liber Entstehung von Doppelbildimo-en, AViirzburg, 

1901. 

Spermann: Exper. Erzeiis:. zweikopfiirer Embrvouen. Sitzber. d. phvs.-med. Ges., 
1900. 

Wetzel: Drei abuorm gebildete Eier. Anat. Anz.. xviii., 1900. 
Wiedemann: Entstelmng d. Doppelbildungen. Virch. Arch.. 138 Bd., 1894 (Lit.). 
See also § 130. 



H. The Different Forms of flalformations in flan. 

1. Aeeests of Development in a Single Individual. 



(a) Ai-rest of the DereJopment o f the Entire EmlrrijonaJ Anlage. 

§ 133. An arrest in the development of the entire embryonal 
anlage manifests itself in two ways. If the distnrbance is very marked. 

a further development of 
the embryo is impossible, 

and it either dies at once 
or becomes stunted, and 
after a certain time per- 
ishes. If the disturbance 
is less severe there develops 
a normally formed foetus, 
but it remains small and 
stunted — that is, a dwarf 
is formed (nanosomia or 
microsomia) . 

A dead foetus is in the 
majority of cases exx^elled 
together with its mem- 
branes (abortion). In 
other cases in which the 
embryo for some cause or 
other remains stationary in 
development, the egg may 
remain for weeks or even 
months in the uterus and 
increase in size, so that 
there arises a disproiDortion between the size of the embryo and of the 
egg. According to His. the first changes after death are shown in a marked 
swelling of the central nervous organs, leading to changes in the con- 




FlG. 333.— Portion of a bvdatid mole. Natural size. 



ARREST OF FCETAL DEVELOPMENT. 



497 



figuration of the head. Later there occurs au infiltration of the tissues 
with wandering cells, the boundaries of the organs become indistinct, 
the entire embryo becomes cloudy and soft, the superficial structure 






breaking through the uterine portion ol a tube into tne aoaommdi tav ny 

indistinct, and the embryo finally becomes completely dissolved Ac- 
cording to Berlet and Engel the wandering -eel J s infiltrating the tissue 
arise in the embryo itself, and indeed from its blood. 

The membranes remaining in the uterus not infrequently suiter patli- 
oloQ'ical changes before their expulsion. Most frequently they form the 
so-called flesh=thrombus or blood=mole- fleshy lumps consisting of the 
membranes and coagulated blood. The blood-clots form the chief 
part of their mass, and are often the cause of the death of tj^f. foetus. 
In the case of the grape= or hydatid mole (Fig. 363) the villi of the 
chorion or placenta sufl"eran extreme hydropic swelling, so that portions 
of the villi become changed into bladder-like structures which are held 
together by delicate connecting strands. The firmer portions of the 
connective tissue are pressed apart by fluid and ultimate y undergo 
liquefaction, especially in the central portions. The epithelium of the 
villi shows in some places evidences of proliferation, m other places 
hydropic degeneration. 

When a foetus well advanced in development dies and remains withm 



49S 



DISTURBANCES OF DEVELOPMENT. 



the maternal organism there may result the formation of a lithopasdion. 
This occurs most frequently in the abnormal situation of the ovum known 
as extrauterine pregnancy, in which the embryo lies in the peritoneal 
cavity, in a tube, or in an ovary. If the foetus dies at such an advanced 
stage of development that it cannot be absorbed, it may be carried within 
the maternal organism for years. Xot infrequently its form is perfectly 
preserved (Fig. 364), and the whole foetus becomes inclosed in a connec- 
tive-tissue membrane. In other cases the foetus, in the course of time, 
becomes converted into a partially huid mass, which contains the osseous 
remains, as well as fat, cholesterin, and pigment, and is surrounded by 
a fibrous capsule. Lime-salts are usually deposited both in the newly 
formed membranes as well as in the portions of the foetus remaining, 
and for this reason the foetus is known as a "stone-child" or "petrified 
child." 

According to the condition of the foetus there may be distinguished 
three chief forms of lithopiiedion (Kiichenmeister). In the first the 
mummified foetus may be easily shelled out from the calcified membranes 
(JitlwceJijphos). In the second form the foetus becomes adherent to the 
membranes at various points which become calcified, while the other 
portions become mummified Qitliocelyplioixedwn). In the third form the 
foetus is discharged, through the rupture of the membranes, into the 
peritoneal cavity, and later becomes encrusted with lime-salts [liihopcedion 
in the narrower sense). 

The long refeniion of a ripe "r even older fatus irithin tht uterus [niisseel Jahof) is rare, 
but may occur (1) in an accessory horn of the uterus, ("2) in interstitial pregnancy, yd) 
after rupture of the uterus. 

Literature. 

(DistiD'hances of Development of tJie Embryo. Liihopcedion. ) 

Bandl: Die Extrauterinschwancrerschaft. Handb. d. Frauenkranklieiten. ii.. Stuttgart, 
1886. 

Eberth: Myxom des Chorion. Virch. Arch.. 39 Bd.. 1867. 

Engel: Ruckbildun2:sv()ro:ano;e an abortiven Embrvonen. Beitr. v. Zie^ler, xxviii., 
1900. 

Giaccomiiii . Entwickelungsanomal. d. menschl. EmbrA-o. Ergebn. d. Anat.. iv.. 1894, 
and loc. cit ^ 130. 

His; Fragen d. path. Embrvologie. Internat. Beitr. Festschr. f. Virchow. i., 1891. 
Kleinwachter : Missed Labor. ^Eulenburg's Realencyklop., v.. 1895 (Lit. l 
Kroemer. Zur Kenntn. der Lithopiidieu. " Munch, nied. Woch.. 1900. 
Kuclienm.eister : Leber Lithopildion. Arch. f. Gyn.. xviii., 1881. 
Mall: Pailiology of Early Human Embr^-os. Johns Hopkins Hosp. Rep . ix., 1900. 
Marchand- Bau der Blasenmole. Zeit. f . Gebh., 38 Bd., 1895 (Lit.). 
Martin Extrauterinscliwangerschaft. Eulenb. Realencyklop., 1895 (Lit.). 
Mliller. H. Leber den Bau der Molen, AViirzburg, 1847. 
Virchow: Die krankh. Geschwiilste. i., 1863. 

Wallenstein: Beitr. z. pathol. Embrvologie. Inaug.-Diss.. Freiburg, 1897. 

(&) Defective Closure of the CerehrospinaJ Canal and the Accompanying 
Malformations of the Xervous System. 

§ 134. Defective closure of the vertebral canal leads to the mal- 
formations known as rachischisis or spina bifida. If the defect in the 
vertebral column is open so that at the bottom of the cleft the bodies of 
the vertebrte covered by membrane are seen, the malformation is ordi- 
narily termed rachischisis. AVhen. at the site of the defect, there is seen 
a protruding sac, the malformation is usually designated sp>ina bifida, or 



RACHISCHISIS. 



499 



more correctly sjyina bifida cystica ; thougli to this formation the names 
rachischisis ci/stica or lujdroracliis cystica may also be api)lied. 

In rachischisis totalis (hoJoracMsckisis) (Fig. 365) the bodies of the 
vertebras form a shallow groove opening posteriorly, and usually covered 
by a thin, transparent membrane ; in rare cases rudiments of the spinal 
cord are still present in the form of whitish bands and lines. In this 
manner there occurs a total or partial amyelia. The defect involves 
principally the motor tracts and centres, as well as the columns of 




Fig. 365.— Craniorachischisis with total absence of the brain and spinal cord. The skull is covered 
witli ragged membranous masses, the-open spinal furrow with a delicate membrane (pia mater). Kypho- 
lordotic' curvature and shortening of the spinal column. Reduced one-sixth. 

Clarke and the lateral cerebellar tract, while the spinal ganglia are devel- 
oped (Manz, Leonowa, K. and G. Petren), and may send sensory fibres 
into the membranous masses of the spinal groove. 

The delicate membrane which lines the furrow and covers the dura 
mater lying beneath it upon the bones is the ventral portion of the 
spinal i^ia mater. A i^artof the nerve-roots may have undergone devel- 
opment, arising either from rudiments of the spinal cord or from spinal 
ganglia. 

Partial rachischisis (meroracMscMsis) involves usually the sacrolum- 
bar or the upper cervical region, while the intervening portions of the 
vertebral column are only rarely the seat of malformations. The dorsal 
surfaces of the bodies of the vertebrae whose arches remain rudimentary 
are covered for the greater i^ai^t by a mass of red velvety tissue, which 
lies uj)on a delicate membrane, though the amount of this tissue may be 
very small or may even be wholly wanting. To the outside of this 
tissue-layer, which is not everywhere equally abundant and which dimin- 
ishes at the sides, there comes next a delicate, ti'ausparent, vascular 
membrane ; and next, outside of this, a zone of epidermoidal tissue some- 
what thinner than normal skin, and often covered Avith many hairs, 
separating the reddened central area from the normal skin. 



cOO 



DISTURBANCES OF DEVELOPMENT. 



The soft red tissue lying in the central area is the rudiment of tlie 
malformed spinal cord, and consists of an extremely vascular tissue 
containing more or less numerous i3ortions of the spinal cord, as nerve - 
fibres, ganglion-cells, and glia-cells, and is designated the area meduUo- 
vascuJosa (vou Eecklinghausen). It is sometimes a continuous tissue, at 
other times it is scattered iu bands and patches, and forms only a deli- 
cate veil-like net. Both the cranial and the caudal extremities of this 
median area may end in a distinct furrow, designated respectively as 
the crcDiial and caudal 2)ol a )• fio- row Polgrube, " von Eeckliughauseu) , 
to which the spinal cord is connected anteriorly and in lumbosacral 
rachischisis the filum terminate caudally. The membrane on which the 
area lies is the pia mater, which also continues into the red marginal 
zone above mentioned, which, being covered with epithelium, is desig- 
nated as the zona epltheJoserosa (vou Eeckliughauseu ). The i^rominent 
zone bordering this and covering the rudiments of the vertebral arches 
is formed of skiu and is known as the zona dermatica. 

On the ventral side of the pia mater forming the covering of tlie 
defect is a space which is bounded below by the dura mater and the ex- 
ternal layer of the arachnoid, so that it is in reality the ventral portion 
of the subarachnoidal space. 

Spina bifida cystica or rachicele (racJiiscJiisis ci/stica) occurs iu three 
chief forms: nti/elomeninc/ocele, meningocele, and myelocystocele. Accord- 
ing to its site there may be further distinguished a cervical, dorsal, lum- 
bar, Itimbosacral, and a sacral spina bifida. In general, a spina bifida 
is characterized by the development of a fluctuating tumor, which is in 
most cases visible externally (Fig. 366) ou the posterior aspect of the 
spiual cohimu {spina bifida posterior) ; but instances also occtir in which 
the sac projects anteriorly from the spinal canal (sp>ina bifida anterior), 
and others in which it is too small to be visible externally (sp>ina bifida 
occulta). 

riyelomeningocele appears most frequently as a S2)ina bifida lumbo- 
sacraUs, and usually forms a tumor v arying in size from that of a nut to 
that of an apple and increasing in size after birth, in the region of the 
lower lumbar and upper sacral vertebn^?. It is covered either by smooth 
or scar-like skin, or may be devoid of skiu on its summit and there cov- 
ered by a reddish, nmcosa-like tissue (area medullovasctilosa). The 




Fig. 366.— Spina biflda saeralis, (After Froriep and Forster.) GM of nineteen years, born with a tuninr 
the size of a piireon's egg over the upper sacral and lower lumbar regions, which enlarged from the sixth 
year on, while at the same time club-feet de\"eloped. 

portiou tmcovered by skin may be drawn in, like a scar. Iu rare cases 
there may be no external tumor (s2)ina bifida occulta), the site of the 
cleft being indicated only by a more marked growth of hair or by a 
depression. 

On oi3eniug the sac, which is composed of the arachnoid (Fig. 367, e) 
and the pia (/', t\), while the dura (r/) does not extend over the dorsal 
portion of the sac, it may be seen that the lower end of the spinal cord 



SPINA BIFIDA. 



501 



(&J is drawn outward, and tliat the cavity of the sac is crossed by nerve- 
roots (/, ij. Occasional nerve -roots (//) may also spring from the colnmns 
of the cord (5 J in its course through the sac. 

According to these findings there is, therefore, an accumulation of 
fluid in the meninges, a hydromeningocele (hydrorachis externa circum- 
scripta), which is combined with a pro- 
lapse of the spinal cord, a myelocele. At 
the site of the protrusion the vertebral 
arches are defective, and this defect may 
reach as far as the hiatus sacralis. 
Smaller defects may involve only one or 
two vertebrae. 

Dorsal and cervical meningoceles are 
much more rare than the lumbosacral. 
The defect in the vertebral arch is usu- 
ally confined to one or two vertebrae. 
The spinal cord is here involved in the 
meningocele in so far that poitions of it 
are drawn outward in the form of a band 
or cone. 

Hydromeningocele spinalis arises 
from a hernial protrusion of spinal arach- 
noid due to a localized collection of fluid 
in the subarachnoidal space. It may oc- 
cur in the first place at the upper end of 
the spinal column in the case of a cleft of 
the upper cervical vertebrae, at the same 
time with hernia of the brain in the oc- 
cipital region. More frequently, how- 
ever, it occurs in the sacral region, where 
the hernial protrusion takes place either 
through a defect in the vertebral arches 
and bodies or through the hiatus sacralis, or between vertebral arches, 
or through intervertebral foramina. In the majority of cases the 
dura takes no part in the formation of the sac, but Adews differ upon 
this point, and by many writers (Hildebrand) a dural sac is described. 
Through a progressive accumulation of fluid the sac may attain a very 
large size. Small meningoceles may be concealed in the deep tissues. 

According to the direction of the hernial protrusion there may be 
distinguished a meningocele posterio7^ and a meningocele anterior, the latter 
taking place through a defect in the bodies of the vertebr£e {rachischisis 
anterior). 

flyelocystocele or hydromyelocele {syringomyelocele) takes its origin 
in a dilatation of the central canal of the spinal cord, as a result of 
which a larger or smaller portion of the cord with its connective -tissue 
envelopes becomes converted into a cystic tumor. The dura is usually 
wanting over that portion of the sac protruding from the vertebrae. 

According to von Recklinghausen, the wall of these sacs is formed 
essentially of the inner spinal meninges, but is lined on the interior by 
a cylindrical epithelium, and has at some part of its inner surface an 
area medullovasculosa — usually on the ventral side, rarely on the dorsal. 
Corresponding to this condition the roots, in case they are still pre- 
served, spring mostly from the ventral, rarely from the dorsal outer wall 
of the sac. The cavity itself is crossed neither by bands nor by nerves. 




Fig. 367.— Myelomeningocele sacralis In 
sagittal section, a little to the left of the 
median line. (After von Recklinghausen.) 
a, skin; b, ?)], spinal cord; c, area me- 
dullovasculosa; d, cranial, d,, caudal 
polar groove ; e, arachnoid ; /, pia, some- 
what separated from the arachnoid; 
portion of pia mater turned over ; g, dura 
mater; /), recurrent roots of the fourth 
lumbar nerve ; i, radix anterior ; I'l, radix 
posterior of the fifth lumbar nerve, run- 
ning free through the arachnoidal sac ; ^, 
sacral nerve-roots between the arachnoid 
and pia ; Z, Slum terminale. 



502 



DISTURBANCES OF DEVELOPMENT. 



Myelocystoceles occui', in the majority of cases, iu lateral clefts of 
the vertebral coluiiiii. TheyshoAv a teudeiic}^ to be combined with defects 
and asiiminctr'u-s of the bodies of the vertebrw, and thereby often Avith 
shortenings of the trunk, which at times affect only the dorsal region, at 
other times also the Inmbar region. Very frequently there exists at the 
same time an exstrophj^ of the abdomen, bladder, and intestine. 

Myelocystoceles are mostly covered only by the outer skin, but are 
sometimes concealed deep down in the soft i^arts. They may further 
be combined with a meningocele, so that a myelocystomeningocele 
arises. 

In cases of rachischisis there sometimes occurs a division of the 
spinal cord into two parts {diastematomyeJia), most often in the case of 
a total rachischisis, in which indeed the rudiments of the spinal cord 
are usually only indicated. In partial rachischisis such division is more 
rare, but the separated strands of spinal cord are better developed, and 
the fibrous and bony coverings maj', at the beginning or end of the cleft, 
send dividing septa between them. Cases have occurred in which each 
cord-half possessed an H -shai^ed area of gray matter. 

The origin of rachischisis is to be referred to agenesia and hypoplasia 
of the medullary folds, which should form the medullary groo\'e of the 
vertebral arches. The agenesia of the spinal cord is also to be dated 
from the very earliest period. Whether it is a primary agenesia i^re- 
determined in the germ, or whether extrinsic injurious influeDces, per- 
haps toxic substances (Hertwig), pressure from without, or the inclosure 
of foetal membranes, may have secondarily checked development or have 
destroyed parts already formed, it is usually difficult to determine ; but 
the symmetrical distribution of the arrested development speaks in favor 
of the former view. 

In cases of S2)ina bifida with hernial protrusion, the local defects in the 
bony vertebral column and the defective development of the dura mater, which 
is usually wanting at the site of the protrusion, are to be regarded as 
the primary condition. The growth of the sac may be explained as due 
to congestive and inflammatory transudation, and many times the residue 
of inflammatory changes, such as thickenings and membranous adhesions, 
may be demonstrated in the pia. 

In the earliest embryonic period the medullar}^ groove is formed by the develop- 
ment on both sides of the median hne of wall-like elevations of the ectoderm which are 
designated as the medullary folds. Through the converging growth and union of the 
latter the medullary groove is closed and formed into the medullar}' canal. Thereupon 
the cell-masses (primitive vertebral plates) lying at the sides of the newly formed canal 
form an envelope about it, which gives rise in the first place to a membranous, non- 
articulated vertebral column. In this, at the beginning of the second month, there 
arise discrete cartilaginous areas from which, in the course of further development, the 
vertebral bodies and arches are formed, Mdiile between them the intervertebral discs 
and vertebral ligaments appear. The developmeni: of the cartilaginous vertebrae is not 
completed until the fourth month, and up to this time the dorsal covering of the med- 
ullary tube consists of the united portions of the membranous vertebral column. The 
cartilaginous constituents of the vertebraj are in the course of development replaced by 
bone. 

According to von Recklinghausen, neither the persistence of a connection between 
the medullary canal and the epiblastnor an excessive stretching of the wall of the med- 
ullary groove through bending of the axis of the embryo can be held responsible for 
the origin of myeloc^'stocele and myelocystomeningocele. According to his view, the 
former is a deficient growth in the long axis of the vertebral column, characterized 
anatomically b}' shortness of the column, absence of vertebrae or parts of vertebne. 
separation of wedge-shaped bony pieces from the bodies of the vertebrae, and by uni- 
lateral defects in the arches. The neural caual, then, in the course of normal de^'elop- 
ment, becomes too long for the vertebral canal, and in consequence becomes ciirled or 



MALFORMATIONS OF VERTEBRAL COLUMN. 



503 



kinked, and there is a tendency to a partial protrusion of the medullary tube at the 
point of sharpest bending. Marchand believes that this hypothesis is not applicable to 
all cases, and Arnold is also of the opinion that the causal relations between arrests of 
development in the muscle-plates and vertebral anlage on the one hand, and those of 
the medullary canal on the other, are not constant, but that a variety of harmful influ- 
ences may give rise to one or more of these anomalies. 

According to 0. Hertwig, the ordinary spina bifida is an arrest of development 
depending upon a partially prevented closure of the blastopore (" Urmundspalte "). 

Literature. 

{Malformations of tJie Spinal Cord and Vertebral Column.) 

D'Ajutolo: Contrib. alio studio delle varieta numeriche delle vertebre, II., Morgagni, 
XXX., 1888. 

Albrecht, P.: Defect der drei letzten Sacral- u. siimmtl. Steisswirbel. Cbl. f. Chir., 
1885. 

Arnold: Myelocyste, Transposition von Gewebskeimen a. Sympodie. Beitr. v. 
Ziegler, xvi., 1894. 

Beneke: Diastematomyelie mit Spina bifida. Beitr. z. path. An., Festschr. f. Wagner, 
Leipzig, 1887. 

Bohnstedt: Spina bifida occulta. Virch. Arch., 140 Bd., 1895. 
Borst: Geschwiilste d. Sacralregion. Cbl. f. allg. Path., ix., 1898 (Lit.) 
Braune: Die Doppelbildungen u. d. anaeb. Geschwiilste d. Kreuzbeingegend., Leipzig, 
1862. 

Brunner: Spina bifida occulta mit Hypertrichosis. Virch. Arch., 129 Bd., 1892. 
Curtius: Spina bifida. Langeubeck's Arch., 47 Bd., 1894. 

Demme: Bericht iiber. d. Thatigk. d. Kiuderspitals, Bern, 1883; Wien. med. Blatter, 
1884, 

Fischer u. Marchand: Ueber d. lumbodorsale Rachiscliisis mit Knickung d. Wirbel- 
silule nebst Mittheilung eines Falles v. Myelocystocele lumbosacralis. Beitr. v, 
Ziegler, v., 1889. 

Forster: Die Missbildungen des Menscheu, 1865, 

Hertwig: Urmund u. Spina bifida. Arch. f. mikr. Anat., 39 Bd., 1892. 
Hildebrand: Spina bifida u. Hirnbriiche. Deut. Zeitschr. f. Chir., 36 Bd., 1893 (Lit.). 
Jacoby : Doppelbildung des embryonalen Riickenmarks. Virch. Arch., 147 Bd., 1897. 
Joaehimsthar. Spina bifida mit localer Hypertrichosis. Virch. Arch., 131 Bd., 1893 
(Lit.). 

Koch, "W. : Beitr. z. Lehre von der Spina bifida, Cassel, 1881. 
Kollmann: Spina bifida u. Canalis neurentericus. Verb. d. Anat. G^s., 1893. 
Kroner u. Marchand: Meningocele sacralis anterior. Arch. f. Gyn., xvii., 1881. 
Lebedeff : Ueber die Entsteliung der Anencephalie u. Spina bifida. Virch. Arch., 86 
Bd., 1881. 

Leonowa : Anencephalie mit Amyelie. Neurol. Cbl. , 1893. 

Manz: Das Auge hirnloser Missgeburten. Virch. Arch., 51 Bd., 1870. 

Marchand: Spina bifida. Eulenburg's Realencyklopadie, xxii., 1899. 

Markoe and Schley: The Sacrococcygeal Dimples, Sinuses and Cysts. Am. Jour. 

of Med. Sc., 1902. 
Meckel: Handb. d. path. Anat., i., Leipzig, 1812. 

Muscatello: Die angeb. Spalten d. Schadels u. d. Wirbelsaule. Langenb. Arch., 47 
Bd., 1894. 

Petren, K. u. G. : Nervensystem bei Anencephalie u. Amyelie. Virch. Arch., 151 
Bd., 1898. 

Pick: Zur Agenesie des Riickenmarks. Arch. f. Psych., viii., 1878. 

V. Reckling-hausen : Untersuchungen liber Spina bifida. Virch. Arch., 105 Bd., 1886. 

Rex: Eigenthlimliche Umbildungen des normalen Wirbeltypus. Prag, Zeitschr. f. 

Heilk., vii., 1835. 
Ribbert: Spina bifida occulta. Virch. Arch., 132 Bd., 1893. 
de Ruyter: Schadel- u. Riickgratsspalten. Langenbeck's Arch., 40 Bd., 1890. 
Saalfeld: Spina bifida occulta mit Hypertrichosis. Virch. Arch., 137 Bd., 1894. 
Sulzer: Spina bifida mit Verdoppelung des Ruckenmarks. Beitr. v. Ziegler, xii., 

1893. 

Taruffi: Delia rachischisi, Bologna, 1890. 

Virchow: Virch. Arch., 27 Bd.; Die krankh. Geschwiilste, i., 1863. 
Wiedersheim : Der Bau des M-enschen, Freiburg, i. B., 1893. 

Wieting-; Ueber Spina bifida u. Zweitheilung d. Rlickenm. Beitr. v. Bruns, xxv,, 
1899. 



504 



DISTURBANCES OF DEVELOPMENT. 



§ 135. Faulty development of the cranium and the associated dis- 
turbances of cerebral development lead to those malformations known 
as cranioscliisis, acrania, liemicrania, microcephalus, anencephalus, exenceph- 
dlus, micrencephaJus, and cepliaJocele. 

Acrania and hemicrania or cranioschisis are the results of an agene- 
sia or hypoplasia of the bony and membranous portions of the cranial 





Fig. 368. 



-Anenceplialia et acrania . Reduced 
one-half. 



Fig. 369.— Cranioscbisis with Exencephalia. 



vault, which arise either as primary disturbances of development or as 
the result of harmful extrinsic influences ux3on the cerebral anlage. 

In acrania both the bony portion and the skin of the cranial vault 
(Pigs. 368, 370) are wholly wanting, the surface of the base of the skull 

being covered only 
^ with a membranous 

vascular tissue. 

If the defect in 
the cranial vault is as- 
sociated with a similar 
defect in the vertebral 
arches, there is pro- 
duced the condition 
known as craniora- 
chischisis (Fig. 365), 
in which the spinal 
column is usually 
shortened and bent, 
the head in conse- 
quence being drawn 
sharj^ly backward and 
the face turned up- 
ward. Through a 

marked bulging of the eyes with deficient development of the forehead, 
these malformations may resemble frogs (frog foetus). 

In hemicrania the flat bones of the cranial vault have undergone more 




Fig. 370.— Partial agenesia of the bones of the cranium in anence- 
phaiia. a. Defect ; b, squamous portion of the occipital bone ; c, parietal 
bone ; d, frontal bone. Reduced one-fifth. 



DEFECTS OF THE CRANIUM. 



505 



or less extensive development (Fig. 370, h, c, d) and form a cranial 
cavity, which is small, in that the flat bones of the vault are ele^^ated 
but a short distance above the base of the skull. If the bones of the 
cranium which have undergone an imperfect development yet unite with 
one another as under normal conditions, there is produced a simple 
microcephalus, which may be present at birth or develop later, as the 
result of imperfect development of the skull. 

Acraniaand hemicrania are often associated with total anencephalus, 
the base of the skull being covered only with a membranous, vascular, 
spongy mass, which is usually composed of vascular connective tissue 
containing scattered haemorrhages, and showing no trace of brain tissue 
or only undeveloped rudiments (area cerebrovasculosa). 

In other cases the meninges contain, besides cystic cavities and gland - 
like remnants of the medullary plate, also more or less developed brain- 




FiG. 371.— Hydrencephalocele occipitalis. Fig. 372.— Encephalomeningocele nasofrontalis. 

substance, which usually protrudes through the defect in the cranial 
vault, giving rise to exencephalus (Figs. 359, 369). The hernial masses 
are either inclosed only by a soft membrane corresponding to the inner 
meninges, or they may be covered also by external skin. 

With microcephalus there is also micrencephalus— that is, an abnor- 
mal smallness of the brain. The development of the brain is also usu- 
ally deficient, or certain portions may be lacking. 

If the cranium is in general closed, but presents partial defects, 
portions of the cranial contents may protrude externally in the form of 
a hernial sac. Such a condition is known as hernia cerebri or cephalo- 
cele (Figs. 371, 372). Defects of ossification (Ackermann), as well as 
a local weakening of the membranous cranial envelope, are doubtless 
the primary cause, though adhesions of the meninges with the amnion 
may also be a cause (St. -Hilaire). The dura mater is wanting over the 
extracranial portion of the sac (Muscatello). 

The size of the protruding sac varies greatly ; it may be so small as 
to be found only after careful examination, or it may be so large as to 
approach the brain in volume. If only the arachnoid and pia protrude 
as the result of a collection of fluid in the subarachnoidal space, the 
hernia is designated a meningocele. If at the same time there is a pro- 
trusion of brain -substance, it is known as meningoencephalocele. A 
hernia of brain -substance and pia without a collection of fluid is an 
enceplialoceie ; if the protruding brain -substance contains a portion of a 
ventricle filled with fluid, it is designated a hydrencephalocele. 

Cerebral hernias occur chiefly in the occipital region (hernia occipi- 
talis), close above the foramen magnum (Fig. 371), and at the root of 



506 



DISTURBANCES OF DEVELOPMENT. 




FIG. 373. 



-Synophtlialmos or cy- 
clopia. 



the nose {hernia sij)ici2)itaJis). In the latter region it may at one time 
involve chiefly the frontal bone (hernia nasofrontaJis, Fig. 372), at 

another time the ethmoid (hernia nasoethinoid- 
aJis) or the lachrymal bone (hernia naso-orhit- 
aJis). More rarely hernias occnr on the sides 
of the sknll (hernia lateralis) or at the base of 
the sknll (hernia hasalis). The latter may 
bnlge toward the nasoj^harynx (hernia spheno- 
pharyngea), or into the orbit (hernia spheno-orhit- 
Yk' 'W ^WMJ'fM «?^*^'), or into the fossa sphenomaxillarisX^mzm 

WmmB S2)henoinaxiUaris). 

In the case of a central hernia the brain 
may be either normal or more or less mal- 
formed. As a result of a marked stunting of 
development, i)articularly in the region of the 
foremost of the three cerebral vesicles, the cere- 
brum may remain single, while at the same 
time a deficient separation of the ocular vesicles 
tal^es place (cyclencephalia or eyclocex)halia of St. - 
Hilaire). In severe grades of this form of disturbance of development 
only one eye may be formed, lying in the middle of the forehead, or 
two eyes united together may 
be found in one orbital cavity 
(Fig. 373), so that the mal- 
formation may be designated 
cyclopia, or synophthalmus, 
and as arrhinencephalus 
(Kundrat). The nose is also 
stunted (Fig. 373) and forms 
a proboscis -like cutaneous tag 
attached above the eye, and 
devoid of bony foundation 
(ethmoeexyhcdia) . 

When the eyes are sepa- 
rate, yet abnormally close to- 
gether, the nose in general 
may be normal, though very 
small at the root (cehocejyha- 
lia). 

In the more severe grades 
of these malformations the 
ethmoid bone and nasal sep- 
tum may be wanting, and the 
upper lip and palate may be 
cleft in the median line, on 
one or both sides (Kundrat). 
In the lighter grades the fore- 
head is merely reduced in size 
and sharply pointed like a 
wedge. 

In the severe forms of 
these malformations the cerebrum consists of a sac (Fig. 374, /, i), oc- 
cupying more or less of the cranial cavity and filled with a clear fluid ; 
at those points where the sac does not touch the cranial wall the inter- 




FiG. 374.— Cranial cavity of a synophthalmus microstomus 
opened by a frontal section (seen from behind), a. Skin 
and subcutaneous tissue ; Z>, cranium ; c, dura mater ; d, 
tentorium ; c, arachnoid ; /, posterior surface of the cere- 
brum, consisting of a thin-walled sac covered by pia mater ; 
g, swollen edge of cerebral sac ; subarachnoidal space 
behind the cerebral sac ; ?, cavity of the cerebral sac, com- 
municating with the subarachnoidal space through the en- 
larged transverse fissure ; /t", section through the corpora 
quadrigemina ; Z, section through the cerebellum ; m, atlas. 
Seven-tenths natural size. 



DEFECTS OF THE CRANIUM. 



veiling space is filled by fluid distending the subarachnoidal space (h). 
In the less marked forms only individual portions of the brain are 
undeveloped, those parts chiefly affected being the olfactory lobes and 
nerves, the corpus callosuiii, a part of the convolutions, etc. The optic 
thalami are often blended together. The chiasm and the optic tract may 
be absent or present. The corj)ora quadrigemina (Jc), pons, medulla 
oblongata, and cerebellum (I) are usually unaffected. 

The spinal cord and brain arise from the medullary canal. In that portion that is 
to become the brain, the neural canal changes very early into three vesicles. The most 
anterior of these, the forebrain, throws out from its lateral portions the primary optic 
vesicles, while the middle portion grows forward and upward and divides into the 
telencephalon or forebrain, and the diencephalon {thalamencephalon) or tweenbrain. From 
the former are developed the cerebral hemispheres, corpora striata, corpus callosum, 
and the fornix. From the tweenbrain are formed the optic thalami and the tloor of 
the third ventricle. The second vesicle or midbrain forms the corpora quadrigemina, 
while the third vesicle divides into the isthmus, metencephalon, and myelencephalon, 
from which there are developed the pons, cerebellum, and medulla oblongata. 

The cerebral portion of the medullar}^ canal becomes inclosed b}'^ the primitive 
vertebral plates of the head, which form the membranous primitive skull, the basal 
portions of which become cartilaginous in the second month of foetal life. In the third 
month the basal cartilage and the membranous vault begin to ossify. 

According to G. St.-Hilaire, Forster, and Panum, acrania and anencephalus are to 
be referred to an abnormal accumulation of fluid in the cerebral vesicles, a hydrocejjhalus, 
occurring before the fourth month. Dareste and Perls oppose this view, and point out 
that in acrania the base of the skull is usually bulged inward and not pressed outward. 
They therefore seek the cause of acrania in a pressure exerted upon the cranium from 
without {Perls), due to an abnormal tightness of the cephalic cap of the amnion, which 
retards the development of the cranium. Lehedeff seeks the cause of acrania in an 
abnormally sharp bending of the body of the embryo, which he thinks occurs w^hen the 
cephalic end of the embryo grows abnormally in the longitudinal axis, or in case the 
cephalic covering lags behind in its development. 

By the sharp bending the change of the medullary groove into the medullary canal 
is thought to be hindered, or the canal after its formation is destro5^ed. From this 
could be explained the later absence of the brain, as well as of the membranous and 
osseous cranial covering. The cystic formations in the membranes lying upon the 
base of the skull are, according to Lehedeff, formed from the folds of the medullary 
plate, which sink into the mesoderm and are then snared off. 

Ilertwig thinks it possible that chemical substances circulating in the blood or 
secreted from the wall of the uterus may destroy the anlage of the brain. 

It is very probable that acrania does not always arise in the same way, and while 
in one case the influences brought forward by Perls and Lehedeff, or also adhesions with 
the fretal membranes, may hinder the development of the skull and brain, it is probable 
that in other cases the malformation must be regarded as a primar}^ agenesia, the 
causes of which were already present in the germ. 

According to K. and A. Petren, the spinal ganglia in anencephalus are always nor- 
mally developed; on the other hand, the columns of Clarke, the lateral cerebellar tracts, 
and the bundles of Gowers are either wholly wanting or are imperfectly developed. 
Likewise the pyramidal tracts are wanting, wiiile the"anterior-horn ganglion-cells and 
the anterior roots are developed. K. and A. Petren, therefore, regard the malformation 
as a system -defect in which the neurones of the second order are not formed ; and they 
incline to the view that the malformation is to be referred to an abnormal anlage of 
the germ. 

Literature. 

{Defects of the Cranium, Cerebral Hernia.^ 

Ackermann: Die Schadeldifformitat bei der Encephalocele congenita, Halle-a.-S., 
1881. 

Arnold: Gehirn, Ruckenmark u. Schadel eines Hemicephalus. Beitr. v. Ziegler, xi., 
1892. 

Beneke: Zwei Falle von multiplen Hirnhernien. Virch. Arch., 119 Bd., 1890. 
Berger: L'origine et le mode de developpement de certaines encephaloceles. Rev. de 
chir., 1890. 



508 



DISTURBANCES OF DEVELOPMENT. 



Ernst: Bildungsfehler d. Centralnervensystems bei Encephalocele. Beitr. v. Ziegler, 
XXV., 1899. 

Forster: Missbildimgen des Mensclien, Jena, 1865. 

Fridolin; Ueber defecte Schadel. Vircli. Arch., 116 Bd., 1889. 

Jacoby : Partielle Anenceplialie bei einem Embryo. Virch. Arch., 147 Bd., 1897. 

Kundrat: Die Arrhinencephalie, Graz, 1882. 

Lebedeff: Entstehung d. Auencephalie u. Spina bifida. Virch. Arch., 86 Bd., 1881. 
Leonowa: Anencephalie. Arch. f. Anat., 1890. 

Manz ; Das Auge hirnloser Missgeburten. Virch. Arch., 51 Bd., 1870. 
Muhr; Encephalocele anterior. Arch. f. Psych., viii., 1878, 

Mucatello: ]3ieangeb. Spalten des Schadels. Langenbeck's Arch., 47 Bd., 1894 (Lit.). 
Petren, K. u. G. : Nervensystem bei Anencephalie u. Amyelie. Virch. Arch., 151 Bd., 
1898 (Lit.). 

de Ruyter: Schadel- und Riickgratsspalten. Langenbeck's Arch., 40 Bd., 1890. 
Schiirhoff: Anatomic d. Centralnervensystems bei Hemicephalen, Stuttgart, 1894. 
Siegenbeek van Heukelom: Encephalocele. Arch. f. Entwickelungsmech., iv., 
1896. 

Spring-: Monographic de la hernie du cervean, Bruxelles, 1853. 
Talko: Ueber angeborene Hirnhernien. Virch. Arch., 50 Bd., 1870. 
Vircliow: Die krankh. Geschwlilste, i., 1863. 

(c) The Malformations of the Face and Neck. 

§ 136. The development of the face not infrequently suffers disturb- 
ances leading to more or less marked facial malformations, which may 
appear alone or in association with malformations of the cranium. If 
the frontal process and the maxillary processes of the first branchial arch 
remain in a rudimentary state or are destroyed to a marked extent 
pathological processes, there persists at the site of the face an open sinus 
giving rise to the conditions known as aprosopia {absence of the face) 
and schistoprosopia {cleft face), which may also be associated with a 
defective development of the nose and eyes. 

More frequent than these large defects are smaller clefts involving 
the lips, alveolar process of the upper jaw, the upper jaw itself, and the 
hard and soft palates (Fig. 375), which are designated as cheilo=gna= 
thopalatoschisis or ** wolf's jaw.'* This malformation gives rise to a 
communication between the mouth and the nasal cavity (Fig. 375). 
The hard palate is cleft in the part bordering upon the vomer ; the soft 
palate in the median line. In the alveolar process of the upper jaw the 
cleft runs between the canine tooth and the outer incisor or between the 
outer and inner incisors. The malformation may be bilateral or unilat- 
eral, and is sometimes primary and inheritable, at other times acquired 
secondarily, in part as the result of amniotic adhesions (Fig. 359). 

^ot infrequently the cleft involves only special portions of the regions 
mentioned, as the upper lip (harelip, labium leporinum), or, what is 
rarer, only the hard or soft palate. The lightest grades of this form of 
cleft-malformation are represented by a notch or cicatricial line in the lips, 
or by a bifurcation of the uvula. 

Prosoposchisis or oblique facial cleft (Fig. 360) is the designation 
applied to a cleft running obliquely from the mouth to an orbit. It is 
usually associated with malformations of the brain. According to 
Morian, three forms may be distinguished. The first is a cleft beginning 
in the upper lip as a harelip, passing into the nasal cavity, thence 
around the ala nasi toward the orbit, and may extend even beyond the 
latter. The second form likewise begins in the region of a harelip, but 
extends outward from the nose toward the orbit. The third form ex- 
tends from the corner of the mouth, outward through the cheek toward 
the canthus of the eye, and divides the superior maxillary process exter- 



MALFORMATIONS OF FACE AND NECK. 



509 



nally to the canine tooth. A transverse cleft of the eheeJc also occurs, pass- 
ing from the corner of the mouth toward the temporal region. 

riedian facial clefts {nasal cleft) run in the median line involving 
the nose, upper jaw, and also the lower jaw, and may extend as far 
down as the sternum. The tongue may also be cleft ( Wolfler). Further, 
the defect may extend even to the frontal bone and brain. 

All of the above-mentioned clefts may be confined to small portions 
of the regions mentioned, and moreover attain varying depths. 

If the development of the inferior maxillary process of the first 
branchial arch is retarded, the inferior maxilla also is imperfectly devel- 
oped or wholly wanting, and there arise those malformations known as 
brachygnathia or agnathia (Fig. 376). The lower portion of the face 



appears as if cut away ; the ears are sometimes brought so close to each 
other as to touch (synotia). Usually the superior maxillary processes 
are also imperfectly developed ; not infrequently the ear is malformed. 

Abnormal largeness of the mouth (macrostomia) , abnormal smallness 
(microstomia), closure (atresia oris), and duplication of the mouth (dis- 
tomia) are all rare. 

When the embryonic external branchial clefts or internal branchial 
pockets fail in part to close, there persist fistulse opening either exter- 
nally or internally, or closed cysts. The former condition is known as 
fistula colli congenita. The mouths of the external fistulse are usually 
found at the side of the neck, more rarely nearer to the median line or 
in the median line ; those of the internal fistulse open into the pharynx, 
trachea, or larynx. Very often the remains of the branchial pockets 
form only diverticula of the last-named organs. The fistulse are for the 
chief part covered with mucous epithelium, sometimes ciliated, arising 
therefore from the visceral branchial pockets, according to von Kos- 
tanecki and von Mielecki usually from the second. In rare cases there 
is found a complete branchial fistula with both external and internal 
openings. 

The branchial cysts arising from the branchial pockets are some- 




FiG. 375.— Double cheilo-ffnathopalatoschisis. 
(Wolf's jaw.) 



Fig. 376.— Agnathia and synotia. 
(After Guardan.) 



510 



DISTURBANCES OF DEVELOPMENT. 



times covered with mucous epithelium (ciliated epithelium) and contain 
fluid; hence they are called hydrocele colli congenita. At other times they 
possess an epidermoidal covering and inclose epidermoidal cell -masses, 
and are therefore classed with the atheromata and dermoid cysts. Dis- 
turbances of development of the anterior end of the branchial arch 
(mesobranchial field) and in the region of the third branchial i)Ocket 
(thymus-anlage) and branchial cleft may lead to the formation of der- 
moids in the snhmentcd region, in the root of the tongue, and in the medias- 
tinum. 

The face and neck are developed in part from a single anlage, and in part from 
paired anlage. The latter are represented in the branchial or visceral arches growing 
from the lateral portions of the base of the skull ventrally in the primitive throat-wall. 
The single anlage, designated the frontal process, is a prolongation downward of the 
base and vault of the cranium, and is, in fact, nothing more tlian the anterior end of 
the skull. Between the individual branchial arches there are at a certain period cleft- 
like depressions known as the branchial pockets. 

The frontal process and the first branchial arch form the boundaries of the great 
primitive mouth-opening, which has a diamond shape. In the course of development 
the first branchial arch sends out two processes, the shorter of which applies itself to 
the under surface of the anterior portion of the head and forms the upper jaw, while 
from the longer one the lower jaw is developed. The frontal process, which forms the 
anterior boundary, gives rise to a broad prolongation of the forehead, and then pushes 
on two lateral processes which are known as the lateral nasal processes. By further 
differentiation of the central portion of the frontal process proper, the septum narium 
is formed, which by means of two spurs, the inner nasal processes, produces the borders 
of the external nasal openmg and the nasal furrow. The lateral nasal processes are the 
lateral portions of the skull, and later develop within themselves the ethmoid labyrinth, 
the cartilaginous roof, and the sides of the anterior portion of the nares. At a certain 
stage they form with the superior maxillary process a furrow running from the nasal 
furrow to the eye, the lachrymal fissure. 

In the beginning the mouth is simply a large sinus, but is soon separated into a 
lower and larger digestive and an upper and smaller respiratory portion. This separa- 
tion is brought about by the development, from the superior maxillary processes of the 
first branchial arch, of the palatal plates, Avhich from the eighth week on blend into 
each other and at the same time unite Avith the lower border of the nasal septum. The 
union of the anterior portions of the palatal plates takes place earlier than that of the 
posterior portions. 

Through the union of the contiguous portions of the frontal and nasal processes 
with the superior maxillary processes the cheek is formed and a continuous superior 
maxillar}' border, from which are developed later the lip and the alveolar process of 
the upper jaw and intermaxillary bones, while the external portion of the nose devel- 
ops from the frontal process. The intermaxillar}' bones are developed as independent 
bones, but unite very early with each other and with the upper jaw. 



Literature. 

{Wolfs Jaw; Harelip; Oblique Facial Clefts.) 

AlbrecM: Arch. f. Chir., xxxi. ; Fortschr. d. Med., iii.. 1885; Biol. Cbl., v., 1886. 
Bartels: Ueber vernarbte Lippenspalten. Arch. f. Anat. u. Phys., 1872. 
Biondi: Lippenspalte und deren Complicationen. Vircli. Arch., Ill Bd.. 1888. 
Forster : Die Missbildungen des Menschen, Jena, 1865. 
His : Auatomie menschlicher Embryonen, iii., 1885. 

Kindler; Linksseit. Xasenspalte verbunden mit Defect d. Stirnbeins. Beitr. v. Ziegler, 
vi., 1889. 

Kdlliker, Th. : Ueber das Os intermaxillare u. d. Anatomic d. Hasenscharte u d. 
AVolfsrachens, Halle, 1883; Die einfache Anlage des Zwischenkiefers. Anat. Anz., 
iii.. 1890. 

V. Kostanecki: Missbilduno;en in der Kopf- u. Halssregend. Virch. Arch., 113 Bd., 

1891. ■ ^ 

Kredel Angeb. Kasenspalten. Deut. Zeitschr. f. Chir., 47 Bd., 1898 (Lit.). 
Lannelongue : Du developpement de Tintermaxillaire externe et de son incisive; 

pathogenic des fissures osseuses de la face. Arch, de med. exp., ii., 1890. 



CLEFTS OF THORACIC AND ABDOMINAL WALLS. 



511 



Lexer: Angeb. mediaue Spaltung der Nase. Arch. f. klin. Chir., 62 Bd., 1900. 
Madelung: Unterlippentistel u. seitl. Nasenspalte. Langenbeck's Arch., 37 Bd., 
1889. 

Marwedel; Mediane Spalte der oberen Gesichtshalfte. Virch. Arch., 163 Bd., 1901. 
Merkel: Gesichtsspalte. Topograph. Anatomic, ii. Heft, 1887. 
Morian; Die schrage Gesichtsspalte. Arch. f. Chir., xxxv., 1887. 
Mliller: Die Hasenscharten d. Tlibinger chir. Klinik i. d. J., 1843-85, Tubingen, 1885. 
Nasse: Mediane Nasenspalte. Langenbeck's Arch., 49 Bd., 1895. 
Schmidt: Spaltbildung im Bereiche d. mittl. Stirnfortsatzes. Virch. Arch., 162 Bd., 
1900. 

Stohr: Zur Zwisclienkieferfrage. Arch. f. klin. Chir., xxxi., 1885. 
Taruffi: Casi di meso-rino-schisi. Mem. della R. Acc. delle Sc. dell' Istit. di Bologna, 
1890. 

Warynski: Bee de lievre simple et complexe. Virch. Arch., 112 Bd., 1888. 
Wolfler; Zur Casuistik der medianen Gesichtsspalte. Langenbeck's Arch., 40 Bd., 
1890. 

Wolff: Hasenscharte. Eulenburg's Realencyklop., 1896 (Lit.). 



(Branchial-deft Fishdce and Cysts. ) 

Baumgarten u. Neumann: Fistula colli congenita. Arch. f. klin. Chir., xx., 1870. 
Bidder: Knorpelgeschwulst am Halse. Virch. Arch., 120 Bd., 1890. 
Franke: Blutcysten d. seitl. Halsgegend. Deut. Zeitschr. f. Chir., 28 Bd., 1888 (Lit.). 
Frobenius; Ueber einige angeb. Cvstengeschwillste des Halses. Beitr. v. Ziegler, vi., 
1889. 

Heusinger: Virch. Arch., 29 and 83 Bd. ; Deut. Zeitschr. f. Tliiermed., ii., 1875. 
Konig-: Fistula colli congenita. Langenbeck's Arch., 51 Bd., 1896. 
V. Kostanecki: Zur Kenntn. d. Pharynxdivertikel des Menschen. Virch. Arch., 117 
Bd., 1889. 

V. Kostanecki u. v. Mielecki: Die angeb. Halskiemenfisteln. Virch. Arch., 120 u. 
121 Bd., 1890. 

Nieny : Halskiemenfisteln. Beitr. v. Bruns, 23 Bd., 1899. 
Richard: Geschwlilste der Kiemenspalten. Beitr. v. Bruns, iii., 1888 (Lit.). 
Schlang-e; Fistula colli congenita. Langenbeck's Arch., 46 Bd., 1893. 
Schmidt; Halskiemenfisteln beim Kalbe. Zeitschr. f. Thiermed., i., 1897. 
Striibing". Zur Lehre v. d. congen. Hals-Luftrohrenfisteln. Deut. med. Woch., 1892, 
Virchow: Halskiemenfistel. Virch. Arch., 32 Bd. ; Tiefes auriculares Dermoid. lb., 
35 Bd.. 1866. 

Zahn; Kiemengangsfisteln. Zeitschr. f. Chir., xxii., 1885. 

(d) Faulty Closure of the Abdominal and Thoracic Cavities^ and the Accom- 

pariying Malfoi^mations. 

§ 137. Arrests of development in the formation of the ventral 
body=wall may take place at different iDoiuts and exhibit different grades 
of severity. They occur most frequently in the region of the umbilicus, 
where the closure of the abdominal cavity takes place latest. In the 
case of imperfect development of the abdominal wall at this point, so 
that a more or less extensive area of the abdominal cavity is closed in 
only by the peritoneum and the sheath of the umbilical cord — that is, 
the amnion— which are pushed forward by the abdominal organs (Fig. 
377), there is produced the condition known as omphalocele, or hernia 
funiculi umbilicalis, or umbilical hernia. The umbilical cord is at- 
tached either to the summit or at one side of the hernial sac, and is more 
or less shortened. 

If the anterior abdominal walls either wholly or in part fail to unite, 
there arise those conditions w^hich are designated fissura abdominalis, 
or gastroschisis completa and thoracogastroschisis. These are char- 
acterized by the undeveloped abdominal coverings not having been sepa- 
rated from the amnion, but passing into it. The greater part of the 
abdominal organs lies in a sac formed by the amnion and peritoneum 



512 



DISTURBANCES OF DEVELOPMENT. 



(^eventration). The peritoneum, however, may also be wanting, likewise 
the umbilical cord, and the umbilical vessels m'Aj i^ursue their course to 
the placenta independently. 

A cleft confined to the thorax is called thoracoschisis. Should the 
heart, covered only with pericardium or wholly free, protrude tlirou.ii'h 
an opening in the cardiac region, the condition is designated ectopia 
cordis. 

"V^Tien the failure to close is confined to the region of the sternum, 
the condition is designated fissura sterni. This defect may involve 
either the whole or a part of the sternum, at times affecting the bones, 
at other times only the skin. 

The protrusion of the urinary bladder through a cleft in the abdomi- 
nal wall is known as ectopia vesicae urinariae. 

Clefts of the abdominal wall are not infrequently associated with 
clefts of the iDarts lying behind the wall, not only in the case of large 
clefts (total), but also in the case of smaller ones (partial). AVhen a 
cleft of the lower portion of the abdominal wall is associated with a 
cleft of the urinary bladder, so that the posterior wall of the latter pro- 
trudes through the abdominal fissure (Fig. 378, c), the condition is 

known as fissura, or exstrophia, or inversio 
vesicse urinaria^. Occasionally the pelvic 
girdle and the urethra are also cleft, the latter 
being represented by a groove open anteriorly 
(Fig. 378, e). The exstrophy is then said to 
be complicated by a fissura genitalis and epis= 
padias. 

AAlien an abdominal fissure or an abdominal 
and vesical fissure is combined with a fissure 
of the intestines, there is produced a fissura 
abdominalis intestinalis or vesicointestinalis. 

The intestinal fissure is sit- 
uated in the caecum or be- 
-/Ji\)-As\ ginning of the colon, and 

the mucous membrane of 
the cleft intestine i^rotrudes 
through the opening in the 
same manner as the posterior 
wall of the bladder, so that 
the condition is called ex= 
strophia or inversio intes= 
tini. 

If the omphalomesenteric 
duct does not undergo its 
normal involution, there re- 
mains at the lower end of 
the small intestioe an ap- 
pendix of intestine called 
Meckel's diverticulum, 
which arises per]Dendicularly 
from the outer margin of the 
intestine. It has usually the appearance of a glove-finger, and is either 
free at its end or attached to the umbilical ring, sometimes being dilated 
at its end. In the case of adhesion to the umbilical ring the intestinal 
mucosa may appear at the navel in the form of a tumor {ectopia intestini, 




Fig. 37 



-Hernia funiculi umbilicalis. Reduced to one-tliird. 



CLEFTS OF THORACIC AND ABDOMINAL WALLS. 513 



adenoma iimhilicale). In very rare cases a cyst lined with mucons mem- 
brane may be formed in the abdominal wall (omphalomesenteric cyst). 

Umbilical hernia and clefts of the npper portion of the abdominal 
wall are frequently combined with craniorachischisis, while exstrophy of 
the bladder and intestine is often associated with myelocystocele. Ac- 




fig. 378.— Fissura abdominis et vesicas urinariae in a Rirl eighteen days old. a. Border of the skin ; 
h, peritoneum : c, bladder ; d, small bladder-cavity corresponding to the trigonum : e, trough-like urethra ; 
labia minora. 

cording to von Eecklinghansen, the two malformations are to be regarded 
as coordinated to each other. Further, large abdominal clefts are often 
associated with lordotic and scoliotic curvatures of the spinal column. 

The development of the body-form from the flat embryonic anlage begins by a 
snaring-off of the individual germ-layers from the outer embryonal area, and their fold- 
ing to form two tubes, the body-wall and the alimentary canal. 

The infolding of these laj^ers takes place at the cephalic and caudal ends, as well as 
at the lateral portions of the embryonal anlage, and as the summits of the folds gradu- 
ally grow together from all directions, tliose which form the body -wall produce a tube 
whose cavity finally communicates only at the parietal umbilicus, by means of a 
peduncle-like prolongation, with the cavity of the extra-embryonic portion of the 
blastoderm known at this time as the vitelline membrane. While the lateral and ven- 
tral walls of the embryo are being thus formed, within the body the intestinal furrow 
also closes to form a tube, which is in communication at only one point lying within 
the parietal umbilicus, known as the visceral umbilicus, with the cavity of the umbili- 
cal vesicle, by means of a channel known as the omphalomesenteric duct. 



Literature. 

Clefts of Thoracic and Abdomiiial Walls ; IleckeVs Diverticulum ; Ectopia 

Intestini. ) 

Aschoff: Verhaltniss d. Leber u. d. Zwerchfells z. Nabelschnurbriichen. Virch. 

Arch., 144 Bd., 1896 (Lit.). 
Chaudelux: Observation pour servir a I'histoire de I'exomphale. Arch. d. phys., 

viii., 1881. 

Herzog: Die Rlickbildung des Nabels u. der Nabelgefasse, Miinchen, 1892. 
Klautsch: Bauchspalten. Cbl. allg. Path., vi., 1895. 



514 



DISTURBANCES OF DEVELOPMENT. 



Kiistner: Das Adenom und die Granulationsgescliwulst am Nabel. Arch. f. Gyn., 

ix., 1877; Vircii. Arch., 69 Bd., 1877. 
Preisz; Ueb. d. sog. Nabeladenom. Jahrb. f. Kinderheilk., 33 Bd., 1891. 
V. Recklinghausen: Spina bifida. Virch. Arch., 105 Bd., 1886. 

Rischpler: Drei Falle von Eventration. Arch. f. Entwickelunsgmech. , vi., 1898 (Lit.). 
Sauer: Prolaps eines offenen Meckel'schen Divertikels. Deut. Zeitschr. f. Chir., 44 
Bd., 1897. 

ScMId: Congen. Ektopie der Harnblase. Arb. a. d. path. Institute in Miinchen, 1886. 
Sieg-enbeek van Heukelom : Die Genese der Ektopia ventriculi am Nabel. Virch. 
Arch., Ill Bd., 1888. 

Tillmanns: Angeb. Prolaps der Magenschleimhaiit durch den Nabelring und iiber 
sonstige Geschwiilste und Fisteln des Nabels. Deut. Zeitschr. f. Chir., xviii., 1883, 
Vejas: Eine seltene Missbildung. Virch. Arch., 104 Bd., 1886. 
Zumwinkel: Subcutane Dottergangscyste. Langenbeck's Arch., 40 Bd., 1890. 

(e) Malformations of the External Genitalia and Anus, due to Arrested 

Developmeiit. 

§ 138. Malformations of varying degree of the external genitals may 
be associated with malformations of the abdominal wall, bladder, and 
the internal genital organs, or may occur independently of these. Coni= 
plete absence of the external genitalia occurs most frequently in con- 
nection with other malformations of this region, particularly in the case 
of sireuomelia, yet the region may in general present also a normal 
structure (Fig. 381). The internal genitals are usually also malformed. 

A stunted condition of the penis is not rare, the organ in conse- 
quence coming to resemble more or less the clitoris. This condition is 
usually associated with a hypospadias — that is, the urethra opens on 
the under side of the organ, either beneath the glans, the body or the 
root of the penis (Fig. 379), or finally even behind the scrotum Qiypo- 




FiG. 379.— Hypospadias with stunting of the penis. Fig. 380.— Epispadias. 

Reduced one-fourth. (After Ahlfeld.) 



spadias perineoscrotalis) . These malformations may exist in penises 
otherwise normally developed, and depend upon a partial failure of the 
sexual furrow to close. 

Epispadias (Fig. 380) is that condition in which the urethral opening 
is found upon the dorsum of the penis. It is more rare than hypo- 
spadias, and is dependent upon a defective or delayed closure of the 
pelvis, so that the cloaca, before the closure, becomes divided into an 
intestinal (anal) and a genital opening (Thiersch). Under certain con- 



MALFORMATIONS OF EXTERNAL GENITALIA. 515 

ditions the penis remains cleft throughout its entire length ; at the same 
time a fissure of the bladder and abdomen may be present. 

Hypertrophy of the prepuce is not rare. If the preputial opening 
is narrowed so that the prepuce cannot be drawn back over the glans, 
the condition is designated a hypertro= 
phic phimosis. Total absence of the 
prepuce is rare ; an abnormal shortness 
is more frequent. 

Defective development of the scro= 
tum is usually associated with retention 
of the testicles in the abdominal cav- 
ity or in the inguinal canal, and leads 
to appearances whereby the external 
genital organs of the male come to re- 
semble those of the female, especially so 
when the penis is also stunted. 

^ In the female the clitoris as well as 
the labia majora and minora may show 
a stunted development. Epispadias 
and hypospadias occur also in the fe- 
male sex, the former coincidently with 
a fissure of the abdominal and bladder 
walls (Fig. 378). In hypospadias a 
portion of the posterior wall of the ure- 
thra is lacking, and the urethral open- 
ing may be found at a greater or less 
distance within the vagina. 

Absence of the urethra occurs in 
both sexes (Fig. 381). In girls the 
bladder may open directly into the 
vagina. 

Closure (atresia) of the urethra 

occurs likewise in both sexes, and re- 
sults either from a i)artial defect of the same or from obliteration of 
the orifice. An accumulation of urine in the bladder may lead to a 
marked dilatation of the same (Fig. 381). 

An abnomal narrowness of the urethra may exist in a portion of 
its course or throughout its entire length. Further, its lumen may be 
narrowed as the result of a hypertrophic development of the colliculus 
seminalis. 

In rare cases multiple orifices of the urethra have been observed. 
Further, in men there may be found in the glans penis a blind tube 
lying beside the urethra. 

Atresia ani simplex is a closure of the anus, the intestine being at 
the same time well developed. It may arise from a failure of the ecto- 
derm to fold in at the anal site, or a cloaca already existing and open- 
ing outward may again become closed through subsequent adhesions 
(Frank). If the rectum does not end immediately above the anal mem- 
brane but higher up, there exists in addition to the atresia ani also an 
atresia recti, a malformation which may occur even when the anus is 
well developed. 

When, with absence of the anus, there is also an arrested development 
of the vaginal wall, which grows downward, between the sinus urogeni- 
talis and intestine, to unite with the perineum, there remains a cloaca 




Fig. 381.— Complete absence of the urethra 
and external genitals, with extreme dis- 
tention of the body due to an enormous dil- 
atation of the bladder. Compression and 
stunting of the lower extremities. (In the 
posterior wall of the bladder rudiments of 
portions of the tubes and ovaries were 
found.) 



516 



DISTURBANCES OF DEVELOPMENT. 



in which the siuiis urogeiiitalis and the end of the bowel nnite. In 
other cases there are fonnd fistulous communications between the 
rectum and the bladder or urethra (in boys) on the one hand, or be- 
tween the rectum and the vagina or uterus on the other ^atresia ani 
vesicaJis, urefhraJis, raghuOlH, utcrina'). 

In rare cases the intestine, in the case of anal atresia, may open 
outward by means of external fistulas in the perineum, scrotum, or 
sacrum. 

Literature. 

{Disturbances of Development of the External Genitalia and of the Anus.) 

Bergh: Epispadie. Vircli. Arch.. 61 Bd., 1867. 
Dienst; Atresia ani congenita. Yircli. Arch., 154 Bd., 1898 (Lit.). 
Eppinger: Atresia ani." Prag. med. Woch., 1880. 
Frank: Die angeborene Yerschliessung des Mastdarms, ATieu, 1892. 
Fiirst: Weiljliclie Epispadie mit Xahel-Urachusfistel. Arch. f. Kinderhcilk., xiv., 
1892. 

Gartner; Atresie des Darms. Jahrb. f. Kinderheilk., xx., 1883. 
Goldmann: Hypospadie. Beitr. v. Bruns. xii., 1894 (Lit.). 

Keibel: Entwiclielung v. Harnblase. Harnrohre u. Damm. Yerh. d. Anat. Ges.. 1895. 
Loewy: Cong. Dilatation d. Llarnblase. Prag. med. AYoch.. 1893. 
Mayr: Kloai^enbildung bei Hansthieren. Ergebn. d. allg. Path., iv.. 1899. 
Rasch: Weibhche Epispadie ii. Fissura vesica?. Beitr. v. Brims, xviii., 1897. 
JReichel: Entstehuns- d. 3Iissbild. v. Harnblase u. Harnrohre. Lan2:enb. Arch., 46 
Bd., 1893. 

Roth: Missbildimg-en im Bereiche des Ductus omphalomesentericus. Yirch. Arch., 
86 Bd., 1881. 

Scherer: Imperforation des Anus. Arch. f. Kinderheilk. . xiv.. 1892. 
Schneider: Atresia ani uterina et vesicalis. Arb. her. v. Baumgarten, i., 1892. 
Schwyzer: Atresie der Harnrohre. Arch. f. Gyn.. 43 Bd.. 1892. 
Seidler: Anus vaginalis. Arb. a. d. pathol. Inst, zu Gottingen, Berlin, 1893. 
Thiersch: Entstehung u. Behandlung d. Epispadie. Arch. d. Heilk., x., 1869. 

(/) JIalforniations of the Extremities due to Arrested Development, 

§ 139. Defective development of the extremities is not rare, and is 
to be referred in part to a i^rimary defect of the anlage of an extremity, 
in part to a disturbance in the Liter development of the limbs or the 
bones, and in part to constrictions caused by strands of the foetal mem- 
branes or by loops of the umbilical cord. Furtlier, such defective devel- 
opment of the extremities may also follow malformations of the central 
nervous system. According to the degree of malformation, the following 
different forms may be distinguished: 

(1) Amelus. The extremities are completely absent; in their place 
are found onlv wartv or stump -like rudiments. The trunk is iisually 
well formed (Fig. 382). 

(2) Peromelus. Stunting of all the extremities. 

(3) Fhocomelus. The hands and feet are alone developed and are 
attached directly to the shoulder and pelvis respectively. 

(4) Micromelus (mierobrachius, micropus). The extremities are devel- 
oped, but are abnormally small (Fig. 383). 

(5) Abraehius and Apus. Absence of ui^per extremities with well- 
de^'eloped lower ones, or vice versa. 

(6) Ferobrachius and Peropus. Stunting of the upper or lower ex- 
tremities. 

(7) Jlonobraehius or Monopus. Absence of one of the upper or 
lower extremities. 



MALFORMATIONS OF THE EXTREMITIES. 



517 



(8) Synqms, Sirenomelia, Symmelia. The lower extremities are fused 
together (Figs. 384, 385), and at the same time turned upon their axes 
so that their external aspects are in contact. The pelvis is usually 




Fig, 384.— Sympus upus. 



Fig. 385.— Sympus dipus. 



518 



DISTURBANCES OF DEVELOPMENT. 



defective, as are also the external genitalia, the bladder, nrethra, and 
the anus. At the end of the blended extremities feet may be entirely 




Fig. 386. ■ Fig. 387. Fig. 388, 



Fig. 386,— Absence of femur and fibula. Diminution in the number of phalanges. One-half natural size. 
Fig. 387. — Perodactylism with syndactylism. Left hand of a new-born child. Seven-eighths natural size. 
Fig. 388.— Skiagraph of same hand as in Fig. 387. Seven-eighths natural size. 



wanting (syynpus apits) and only a few toes may be present (Fig. 384) ; 
in other cases (Fig. 385) one (symjms monopus) or both feet may be pres- 
ent (sympus dipus). 




Fig 389. Fig. 390. 

Fig. 389.— Malformation of the right hand, perochirus, with blending of the fingers. (After Otto.) a. 
Supernumerary thumb ; Zi, thumb proper ; c, stunted index finger ; d, middle finger ; 6, ring finger ; /, 
little finger, 

Fig. 390.— Skeleton of the hand (perochirus) shown in Fig. 389, seen from the dorsal side. (After Otto.) 
a-/, as in Fig. 389 ; g, ulna ; h, radius ; i, os naviculare ; 3, os lunatum ; 3, os triangulare ; A, os pisiforme; 
5a, OS multangulum majus superfluum ; 5h, os multangulum ordinarium ; 6', os multangulum minus ; 7, os 
capitatum ; S, os hamatum. 



MALFORMATIONS OF THE EXTREMITIES. 



519 



(9) Absence of individual bones may occur in any part of the extremi- 
ties (Fig. 388). 

(10) Ferodactylism — stunting of the fingers or toes — appears in a great 
variety of forms, but in general is seen as a defective development 
(braclujphalangism) or complete absence of individual phalanges (Figs. 
386, 388, 390, c), or as membranous (Figs. 387, 389) or bony (Figs. 
388, 390, d, e) connections between the fingers {syndactylism). 

If only the outer fingers or toes are developed while the middle ones 
are lacking, there arise those formations (Figs. 391, 392) designated as 
cleft-hand and cleft foot (Kiimmel). In more extensive malformations 




FIG. 391. Fig. 393. 



Fig. 391.— Peropus or cleft-foot. (After Otto.) Right foot, a, Great toe ; 7j, little toe. 

Fig. 392.— Skeleton of the foot in Fig. 391, seen from the dorsal side, a. Great toe; b, little toe; c, 
rudiment of third toe ; d, tibia : e, fibula ; i, talus ; 5, calcaneus ; J, os naviculare ; A, os cuneiforme majus ; 
5, os cuneiforme minus ; 6, os cuneiforme tertium ; 7, os cubiforme. 

of the fingers there occur in part also malformations and defects in the 
region of the tarsal and metatarsal bones (Fig. 392) or carpal and meta- 
carpal bones respectively. These malformations are designated respec- 
tively s^sperojms and perochirus. Absence of the hand or foot is known 
as achirus or apus. 

Literature. 

(Malformations of the Extremities. ) 

Ahelin 11. Blix: Ueber Abschnurung von Gliedern. Jahresber. d. ges. Med., 1863. 
Arnold: Myelocyste, Transposition v, Gewebskeimen u. Sympodie. Beitr. v. Ziegler, 
xvi., 1894. 

Bambeke: Ueber Abscliniirungen von Gliedern, Annal. de la Soc. de med. de Gand, 
1861. 

Basch-. Ueb. d. sog. Flugliautbildung in d. Kniekehle, Zeitsclir. f. Heilk., xii., 1891. 
Billroth: Durcli Knocliendefecte bedingte Verkrlimmungen d. Fusses. Arch. f. klin. 
Chir., i., 1861. 

Bomer: Anat. Unters. eines Kindes mit Phokomelie. Inaug.-Diss., Marburg, 1887. 
Brunner: Genese, congen. Mangel u. rudim. Bildung d. Patella. Virch. Arch., 124 
Bd., 1891. 

Burckhardt: Knochendefecte am Vorderarm u. Unterschenkel. Jahrb. f. Kinder- 
heiik., 81 Bd., 1890. 

Dareste, C. : Mem. sur les anomalies des membres. Journ. de I'anat. et de la phys., 
1882. 



520 



DISTURBANCES OF DEVELOPMENT. 



Ehrlich: Congen. Defecte u. Hemmungsbildungen d. Extremitaten. Vircli. Arch., 
100 Bd. , 1885. 

Fischer: Congen. Defectbildung an d. Unterextremitat eines siebenj. Knaben, Rostock, 
1886. 

Fricke: Ueber congen. Defect der Fibula, Bonn, 1887. 

Gebhardt: Eiu Beitrag zur Anatomic der Sireuenbildungnen (contains anatomical 

study of Figs. 384 and 385). Arcli. f. Anat. u. Pliys., 1888. 
Goldmann. Beitr. z. Lelire v. d. Missbild. d. Extremitaten. Beitr. v. Bruns, vii., 

1891. 

Grisson: Defect d. Oberschenkeldiapbj'se. Langenbeck's Arch., 49 Bd., 1894. 
Gruber: Defecte d. Hand. Arch. f. Anat., 1863; Defect des Radius. Virch. Arch,, 
82, 40 Bd., 1861. 

Hlavaceck: Extremitatenmissbildungen. Deut. Zeitschr. f. Chir., 43 Bd., 1896. 
Joachimsthal : Defecte langer Rolirenknochen. Deut. med. Woch., 1895; Bracliy- 

dactylie u. Hyperphalangie. Virch. Arch., 151 Bd., 1898; Die angeb. Verbildung 

d. ob. Extremitaten, Hamburg, 1900. 
Klaussner: Die Missbildungen der mensclil. Gliedmaassen, Wiesbaden, 1900. 
Kiimmel : Die Missbildungen d. Extremitaten, Kassel, 1895. 
Lotheissen : Mangel d. Oberschenkelknochen. Beitr. v. Bruns, xxiii., 1899. 
Mayer: Spalthand u. Spaltfuss. Beitr. v. Ziegier, xxiii., 1898. 
Melde: Defect der Tibia u. Poly dakty lie. Inaug.-Diss., Marburg, 1892. 
Mies: Angeb. Mangel des V. Fingers u. Mittelhandknochens. Virch. Arch., 121 Bd., 

1890. 
Otto: L. c, § 130. 

Paster; Missbildung der Hande und Fiisse. Virch. Arch., 104 Bd., 1886. 
Pauly; Mangel der Diaphyse u. der unteren Epiphyse d. Tibia. Langenb. Arch., 
xxiv., 1879. 

Pfitzner: Brachyphalangie. Verb. d. anat. Ges., 1898. 

Poelchau: Ein Fall von Perodaktylie. Inaug.-Diss., Konigsberg, 1891. 

Rasch: Syndactylie und Polydactylie. Beitr. v. Bruns, xviii., 1897. 

Rennert: Beitr. zur Kenutniss v. d. Missbildungen der Extremitaten, Leipzig, 1882. 

Rug-e; Sirenenbildung. Virch. Arch., 129 Bd., 1892. 

Schafer: Congen. Defecte von Handen und Fiissen. Beitr. v. Bruns, vii., 1891. 
Steinhaus: Congenitaler Tibiadefect. Virch. Arch., 163 Bd., 1901. 
Steinthal: Ueber angeb. Mangel einzelner Zehen. Virch. Arch., 109 Bd., 1887. 
Strieker: Ueber angeb. Defect des Radius. Virch. Arch., 31 Bd., 1864. 
Teacher and Coats: Siren-malformation. Journ. of Path., iii., 1895. 
Tschudi: Vollst. Verwachsung aller 5 Finger. Zeitschr. f. Chir., 35 Bd., 1893. 
Voigt: Ueber congenitalen Radiusdefect. Arch. d. Heilk., 1863. 



2. Abnormal Position of the Internal Organs and of the 

Extremities. 

§ 140. Of the abnormal positions of the internal organs, the most im- 
portant is the one known as situs inversus viscerum — i.e., a lateral 
transposition of the internal organs, so that the position of the thoracic and 
abdominal organs forms a mirror-image of the normal position. This 
condition has been observed both in double monsters and in single indi- 
viduals. It may be restricted to the heart alone, or to the abdominal 
organs, or more rarely to a part of the latter (situs irregularis), but the 
last is rare. In general, abnormal positions occur especially in the case 
of the abdominal organs. For example, the kidney is not infrequently 
found in an abnormal position (di/stojna renis), usually abnormally low, 
so that it approaches the sacral promontory or lies in front of the same. 
The testis is not rarely retained within the abdominal cavity (ectopia in- 
terna, or abdominalis testis, or cryptorchismus), or within the inguinal canal 
(ectopia ingidnalis), or at the external ring (ectopia pubica), or in the 
fold between the thigh and scrotum (ectopia cruroscrotalis) , or in the peri- 
neal region (ectopia perinealis), or in the fold of the groin (ectopia cru- 
ralis). Abnormal positions of the intestines, particularly of the colon, are 
not rare. 



ABNORMAL POSITION OF ORGANS AND PARTS. 



521 



Among the abDormal positions of the extremities congenital luxa^ 

lions (slipping of the articular heads from their sockets) are of especial 
interest. They are most common at the hip -joint, more rare at the 
elbow-, shoulder- and knee-joints. According to von Amnion, Grawitz, 
Kronlein, and Holtzmanu, the congenital luxations are in part due to 
local arrests of development, but may also be the result of mechanical in- 
fluences. In the case of the hip -joint the disturbance of development 
results in a small and imperfect acetabular socket, and the head of the 
femur is usually more or less imperfectly developed. The small acetab- 
ulum lies in the normal position, but the head of the femur is displaced, 
most often backward (luxatio iliaca). At birth the ligamentum teres is 
always intact, and the capsule of the joint covers both the head of the 
femur and the acetabulum. After much use of the leg the ligamentum 
teres becomes stretched and may tear, the capsule becomes dilated and 
bag-like, and at the point where it is pressed against the bone may be- 
come perforated. A new joint may then be formed through the prolif- 
eration of the surrounding tissues. 

Abnormal positions of the feet and hands are to be referred partly 
to disturbances of development and partly to mechanical influences 
exerted upon the extremities during their growth. The most important 
is congenital club=foot (pes equino varus), which, according to Esch- 
richt, is to be referred to an arrest of development, by which the foot is 
left in the foetal position, with accompanying abnormal development of 
the bones and their articular surfaces. The inner border of the foot is 
sharply elevated, and the foot at the same time brought into plantar 
flexion. The collum tali is elongated in an anterior and inferior direc- 
tion (Hiiter, Adams). If the children thus afflicted learn to walk, they 
tread upon the outer side of the foot, which thereby becomes flattened, 
while the foot becomes still more sharply turned inward. 

Congenital club-foot, though usually to be regarded as a primary dis- 
turbance of development of the affected joint, may also under certain 
conditions be caused by an abnormal pressure due to a relatively small 
uterus (Volkmann). Under these conditions develop also those patho- 
logical positions of the foot known as pes calcaneus and pes valgus, 
which are characterized partly by strong dorsal flexion and partly by 
an outward twisting of the foot. Frequently the evidences of the press- 
ure to which the feet have been subjected are seen in an atrophic con- 
dition of the skin and portions of the bones. 

The position of the hand known as clubbed=hand or talipomanus is 
caused by a rudimentary development of the radius, and is usually asso- 
ciated with other malformations. 

Literature. 

(^Malformations of the Extremities and Internal Organs^ due to Change of 

Position. ) 

V. Ammon: Die congen. cbir. Krankh. d. Menschen, Berlin, 1842. 
Arneill: Transposition of the Viscera. Amer. Jour, of Med. Sc., 1902. 
Bessel-Hagen : Pathologic u. Therapie des Klumpfusses, Heidelberg, 1889. 
Buhl: Transposition d. Eingeweide. Mittheil. a. d. pathol. Inst, zu Miinchen, 1878. 
Debersaques: Pathogenic du pied hot congen. Ann. dc la Soc. de med, deGand,, 
1891. 

Dollinger: Congenitale luxation. Langenbeck's Arch , xx., 1877. 
Geipel: Situs transversus. Festschr. z. 50-jahr. Besteh. d. Krankenhauses, Dresden, 
1«99. 29 



522 



DISTURBANCES OF DEVELOPMENT. 



Grawitz; Ursaclien d. ani^L'b. Hriflgek'nkvcncnkuniicn. Virt-h. Arcli.. 74 Bd.. 1878. 
Hirsch.: Die Entstcliunu' d. anu-eb. 1 liift venx'iikungr Yircli. Arch., 148 Bd.. 1897. 
Holl: Plattfiiss. Langenbcck's Arch., xxv.. 1880." 

Holtzmann; Die Enrstehung d ciuiiicn. Luxationen. Virch. Arc'ii , 140 Bd., 189o. 

KoUer; Situs visceriim inversus. A'irch. Arclr, l.")6 Bd., 1899. 

Kipper: Situs transversus. Inaug.-Diss. . ^larburg, ls96. 

Kirmisson: Cliirurg. Krankliciicn angcb. rrsprungs. Stuttgart, 1899. 

Kocher; Kliimpfuss. Dent. Zciisrlir. f. C'hir., ix., 1870. 

Krdnlein: Luxationen. Dcut. ("liii.. -^G Lief.. 1882. 

Kuclieiimeister : Die anseb. voll.st Verlagerung d. Eino-eweide d. Meuscheu, Leipzig, 
1883. 

Lochte; Zur Kenntn. d. Situs transversus partialis. Beitr. v. Ziegler, xvi., 1S94; 

Situs viscerum iri-egularis, lb., xxiv.,1898. 
Liorenz: Pathologie u. Therapie der augeb. Hiiftverrenkung, Wien, 1895. 
Martinotti .- Delia trasposizione laterale dei visceri. Bologna. 1888. 
Messner; Kuoclien verand. bei Pes calcaneus congen. Arch. t. klin. Cliir., 42 Bd., 1892. 
Michaud; Pied bot congenital. Arch, de pliys, , iii., 1870. 

Miiller; Congen. Luxation im Knie. Arb. a. d. chir. Universitatspolikl. in Leipzig, 
1888. 

Pauly: Plattfuss. Laugeubeck's Arcli. , xxiv., 1879. 

Sonnenburg-: Klumpfuss. Realeuc^vklop. d. med. Wissensch., 1890 (Lit.). 
Wehn: Zur Frage d. Situs transversus. Virch. Arch., 98 Bd., 1884. 

3. Malfoematioxs due to Excessive Gkowth or Multiplica- 
Tioxs OF Okgaxs or Body-parts. 

§ 141. The malformation known as general giant growth occurs as 
the result of an excessive growth of the entire body, either during intra- 
uterine life or later. During extra- uterine life such an abnormal growtli 
may occur that the size of the affected individual may far exceed the 
maximum normal limits. 

Partial giant growth may also take place during intra-uterine life or 
after birth. The head and portions of the extremities are usually af- 
fected. A unilaferaJ f/iaiit f/rowfh is usually restricted to the half of the 
face or to one extremity, but in vei y rare cases the hypertrophy may in- 
volve all the parts of one side: face, trunk, and extremities. In extra- 
uterine life trauma sometimes gives tlie iinpulse to a pathological excess 
of growth. 

In the pathological hypertrophy of an extremity, or of a portion of 
the same, as a finger, the structure of the part may in general i)reserve 
its normal relations, in that all the constituent tissues participate in the 
increased growth. In other cases the tissues are not equally involved, 
so that, for example, the soft parts, particularly the fat tissue, may be- 
come especially increased in amount. Further, the enlarged soft parts 
of the extremities often show a pathological structure, containing, for 
example, abnormally developed blood- and lymph-vessels. AYhen the 
extremities are disfigured as the result of sucli an increase of tissue, the 
condition is usually called elephantiasis. If the thickened areas are 
sharply circumscribed, the formations are regarded as tumors, and, ac- 
cording to their structure, are classed with the angiomata, lymphangio- 
mata, and fibromata (see §§ 103, 108, 109). On" the trunk the local 
excesses of tissue-growth occur 7iiost frequently in the form of elephan- 
tiasis-like formations, or as tumors. The same is true of such growths 
of the soft parts of the face ; the lips, dieeks, and tongue not infre- 
quently being more or less enlarged and disfigured through the forma- 
tion of connective-tissue hyperi)lasias lichly supplied with lymphatic 
vessels. 

Circumscribed hyi)ertroi)hies of the bones occur in various portions 



MALFORMATIONS DUE TO EXCESSIVE GROWTH. 



523 



of the skeleton, and iiie .somelinies iiinltii)le. The bones of the skull 
as well as those of the faee may be thus atfected, and there occur cases 
in which the hypei'troi>hy of the bone may be so extensive that one or 
both of these regions may show marked disfiguration, and there are pro- 
duced conditions ^\ liich are known under the general term of leontiasls 
ossea (Fig. 126). C'ii'cumscribed hypertrophies of the bones lead to the 
formation of osteomata or exostoses, which are often multiple. On the 
trunk and extremities local growths of bone may lead to the enlargement 
of single bones as well as to the formatioji of atypical exci'escences 
known as osteomata and exostoses, which are not infrequently multiple. 

Literature. 

(Giautism.) 

Andersen, Riesonwiiclis dev Extremitateu. St. Thorn. Hosp. Rep., Londou, 1882. 
Arnheim. Congeuitale Ijalbseitige Hypertrophie. Vircli. Arch,, 156 Bd., 1898 (Lit.). 
Bessel-Hagen . Part, Rieseuwuclis u. multiple Exostoseii. Langenbeck's Arch., 41 
Bd., 1891. 

Buhl: Ehi Riese niit Hyperostose, Mitth, a. d. path. Inst. Miiuchen, 1878. 
Busch: Riesenwuchs dcr Extreinitaten. Arch. f. kiln. Chir, , vii., 1866. 
Curling-: Riesenwuchs der Finger. Med. -Chir. Trans , xxviii., 1845. 
Ewald; Hypertrophic der Hand Virch, Arch.. 36 Bd , 1873. 
Fischer: Riesenwuchs der Extremitaten. Dent. Zeitschr. f. Chir., xii., 1880. 
Frankel: Makrosomia. Virch. Arch , 46 Bd., 1869. 
Friedberg-: Riesenwuchs der Extremitaten. Ib..40Bd., 1867. 
Friedrich; Halbseitige congenitale Kojifhypertrophie. lb , 28 Bd , 1863. 
Gruber; Makrodaktylie. lb., 36 Bd., 1872' 

Kessler: Ueber einen Fall von Makropodia lipomatosa. Inaug,-Diss , Halle, 1869. 
Little: Riesenwuchs der Extiemitaten. Trans. Path. Soc. , 1866. 
Trelat et Monod: Dc 1 'hypertrophic unilaterale. Arch. gen. de med., 1869, 
Vierordt, H. : Anatom., physiol. u. physikal, Dateu u. Tabelleu, Jena, 1893. 
See also § 77. 

§ 142. The occurrence of supernumerary organs, oi' of a multipli= 
cation of parts of the skeleton, and of the muscular system, is relatively 
frequent. Such phenomena are to be attributed in part to a cleavage or 
multiple appearance of the given anlage, and in part to a more marked 
development or persistence of organs which normally remain in a rudi- 
mentary state, or undergo retrogression during the period of growth. 
Further, certain of the conditions included under this head may be re- 
garded as reversions. 

1. Duplications of the extremities. A duplication of an entire ex- 
tremity without the duplication of the pelvic or shoulder bones has not 
been observed in man. Duplication of the hands and feet is very rare 
(Fig. 393), but a number of cases are reported in the literature. The 
number of fingers may reach nine or ten. 

Much more frequent is a multiplication of the fingers (polydactyl 
ism) on a single hand (or foot respectively), in which condition the super- 
numerary fingers (or toes) are attached in part at the ulnar or radial side 
(or tibial and fibular sides respectively), or in part intercalated between 
the others (Figs. 390, a; 394). Often the fingers are duplicated only in 
part — that is, by the cleavage of the first or the first and second terminal 
joints (Figs. 395, 396). Those attached at the margin of the hand may 
be well developed (Fig. 394) or rudimentary. Occasionally they appear 
as small pedunculated fibrous tumors. In the fully developed suiter 
numei ai'v fingers or toes the phalanges (Fig. 394) may articulate with 
the metacarpal or metatarsal bones of a neighboring finger or toe, or with 



524 



DISTURBANCES OF DEVELOPMENT. 



their own (supernumerary) carpal or tarsal bones (Fig. 390, 5a). Poly- 
dactylisni in certain cases is inherited and is therefore dependent upon 
intrinsic causes. A duplication of 
a finger may also occur through 
cleavage of the anlage under the in- 
fluence of intra-uterine influences, 

and is consequently not inheritable. ^ \ i [ ( >a 





Fig. 393. 



Fig. 394. 



Fig. 393.— Polydactylism with forking of the hand. (After Lancereaux.) 

Fig. 394.— Polydactylism in a new-born child. Skeleton. Duplication of the phalanges of the fourth 
and fifth fingers. Natural size. 





Fig. 395. Fig. 396. 

Fig. 395.— Polydactylism and syndactylism of the left hand. Reduced one-fifth. 
Fig. 396.— Polydactylism and syndactylism of the right foot. Reduced one-fifth. 



SUPERNUMERARY ORGANS OR PARTS. 



525 



2. Supernumerary nipples and breasts (hyperthelia, hyper= 
mastia) are not uiicomnion malformations in both sexes, and are prob- 
ably to be regarded as a reversion to polymastic racial ancestors. The 
supernumerary organs are usually situated on the thorax, along two lines 
converging from the axillary to the inguinal regions, but in rare cases 
they may be found elsewhere — in the axilla, on the shoulder, on the 
abdomen, back or thigh. They are usually small, but in the event of 
pregnancy may take on functional activity. The number of the nipples 
may reach as high as ten. 

8. The formation in men of breasts resembling those of women 
(gynsecomastia) is rarely seen in well-developed men with normal sex- 
ual apparatus (see Hermaphrodism, § 143), but it not infrequently hap- 
pens that the male breast undergoes a moderate enlargement at the time 
of puberty. 

4. Duplication of the penis is of very rare occurrence, and may be 
associated with the formation of two urethrse having independent open- 
ings into the bladder, and with two scrota, the two penises being typi- 
cally developed (Lauge). 

5. Supernumerary bones and muscles are of frequent occurrence. 
Supernumerary vertehrce may be found in any part of the spinal column ; 
and at its lower end may in rare cases cause a lengthening of the column, 
resulting in the formation of a tail. According to Virchow, three forms 
of tails may be distinguished : true tails containing bones ; false or im- 
perfect tails which represent an elongation of the vertebral column, 
but contain neither cartilage nor bones (so-called i)ig's-tail) ; and tail-like 
appendages of skin which consist of different forms of tissue, and in part 
are to be classed with the teratomata. The true tails are very rare; ac- 
cording to Bartels, they are more often the result of a separation or 
elongation of the vertebrje than of an increase in their number. 

Supernumerary ribs in the neck or lumbar region, as well as a forking 
of the ribs, are not I'are. 

Supernumerary teeth also occur. 

6. Duplication or cleavage of the anlage of the thoracic and ab- 
dominal organs occurs most frequently in the case of the spleen, pan- 
creas, adrenals, ureters, pelvis of the kidneys, and lungs, more rarely in 
case of the ovary, liver, kidney, testicle, and bladder. 

Literature. 

{Supernumerary Organs or Parts. ) 

D'Ajutolo: Contrib. alio studio delle varieta numenche delle vertebre. II Morgagni, 
XXX., 1888. 

Ammon: Die angeb. chiriirg. Krankheiten, Berlin, 1842. 
Bartels. Scliwanzbildung. Arch. f. Anthrop., 15 Bd., 1884. 
Beer : Beitr. z. d. Lehre v. d. Missgeburten. Inaug. Diss., Ziiricli, 1850. 
Boinet: Polydactylie et atavisme. Rev. de med., xviii., 1898. 
Bonnet: Die Mammaorgane. Ergebn. d, Anat., ii., Wiesbaden, 1893. 
Buschan: Polyniastie. Eiilenburg's Realencyklop., xix., 1898 (Lit.). 
Ecker; Scliwanzbildung. Arch. f. Anthrop., xi. ; Arch. f. Anat., 1880. 
Freund: Scliwanzbildung beini Menschen, Virch. Arch., 104 Bd., 1886. 
Gegenbaur: Krit. Bemerkungen iiber Polydaktylie als Atavismus. Morph. Jalirb., 
1880. 

Gerlach: Schwanzbildung. Morph. Jahrb., vi. 

Habs: Makrodaktylie. Deut. Zeitschr. f. Chir., 37 Bd., 1893. 

Hennig u. RaubeV: Ein Fall von geschwanztem Menschen. Virch. Arch., 105 Bd., 
1886. 



520 



DISTURB A XCE;^ OF DEVELOPMENT. 



Joach.imsth.al- Ilyix-riilialanuic A'irc)]. Arcli., lol J](l. ; Die anirt'l). Yerbild. d. ob. 

Extreiiiitat. Ilainbiiru. 1900. 
Jolly: Polvdaktvlie 111. Missl)il(l. d. Anns. Int. Jjciir.. Fcstsclir f. Vircli. i.. Ik^rliu, 

1891. 

Klaussner : Ueber ]\Iissl)il(lung'.ni d. nuMischl. Glicdiriaasscii. Wiesbaden, 1900. 
Kohlbrug-g-e : Sclnvanzbiltlunii- u. Sieissdrlise. Xatuurk. Tijdschr. voor 2sed. lud., 
1S9:. 

Kollmann: Handskelet u. Hyjierdaktylie. Anal. An/... iii.. 1^^^. 
Kiittner; Verdoppelnnu- des Penis. Bein-. v. JJnins, .w.. 1^9(1. 
Lang-e; Complete \'' !<iiu)j)c-]ung des ]\'nis. Beitr. v. Zieuler. x.xiv.. 1898 (Lit.). 
Laurent: Les bi-exu. -. gyneeoniasres et hennaiilii < xiites. Pariv. 1894. 
li eicht en stern ■ Supeinumcrilre Brlisle ii Brustwar/.en. Vireli. Arcli , 73 Bd., 187d 
(Lit.). 

Levin: Ueberzaid. kleine Finger. Yircd). Areli.. 14'3 Bd.. 189."). 
Lissner: Schwanzbildiing beim IMensclien. Vircli. Aicii.. 9'.) Bd . 1^>^T. 
Neugebauer: Polymastie ndt 10 Bnistwai zen. Cbl. t. G\ n . bs^d ; So Fillk^ v. Ver- 

doi:)p. d aiiss. Geniralien. Monatssclir. f. Gebli.. vii.. 1897. 
Otto: Monstrornm sexcentonun desci'iptio anat( miica. 1844. 

Pfitzner: Doj^pelbildung d. ■") Zelie. Alorph. Arl). . 1S9.-) ; A'ei'iloppehing d. Zeigeiingeri?: 

lb., vii.. 1S97; Missbild. d. Extreniitatenskelef s. lb., viii.. ls98. " 
Piatnisky; Ban des meuschliclien Sch wanzes. Inaiiu-.-Diss.. Peiersburi:- : Anat. Auz., 

viii. . 1S93 

Schmidt: Xoimale Hypertbelie menscld. Endjryonen. Anat. Anz.. xi., 1890. 

Sell: Hvperthelie. Hvpermaslie n. Gvnakoniustie. Ber. d. >satnrf. Ges . Freiburg, 

ix. .'l894 (Lit.). 

Stieda. Gynakomastie. Beitr. v. Bums. xiv..l89.-). 

Stahr; Congen. Tumor am kl. Finger. A'ireh. Arch.. 151 Bd., Suppl . 189s. 
Virchow: Schwanzbildiing. Deut. med. ^V()C•ll.. 1SS4. 
Wiedersheim- Der B:iu des 3Iensehen. Freiburg i. B.. 1893. 

Zander: 1st die Polvtlaktvlie theromcridie Varietat ock-r Missbilduuir? Yircli. Arch., 
12.-) Bd., 1S91 



4. Tele axd False Hek.aiaphrodism. 

§ 143. The fact tliat the sexual oigaus, both the sexual ^lands and 
the external genitals, of both sexes. deveh)p from originally similar 
anlage which contain the beginnings of all the sexual i)i'gans of both 
sexes, makes it apriori probal)le that malformations might result through 
unequal development of the anlage of the right and left sides, or through 
a simultaneous development of organs i)eculiar to botli sexes, or finally 
through a lack of harmonious development of the external jnid iiit(M'nal 
genitals. 

Those malformalions which are to be referred to some one of the factors 
named, and which are characterized by the fact that the sexual apparatus 
of a single individual contains parts belonging to l;)oth the male and 
female, are grouped under tli(^ drsiguation hermaphrodismus (Fig. 
397). When both sexual glan(l> it-stis and ovary ) are present the con- 
dition is called hermaphrodismus verus i lif riiiaphrodismu.s glandularis, 
Siegenbeek van Heukeloin). If the t nixing of sexual characteristics 
consi.sts merely of a combination of male and female genital passages 
with the external genitalia of the opposite sex, the condition is kitown as 
p.seudohermaphrodismus. The true sex is determined by the nature of 
the sexual glands. 

The body build of hermaphrodites frequently shoMS a curious mix- 
ture of male and female characteristics. For example, the breasts, neck, 
and shoulders may correspond to the female type, while the develop- 
ment of the beard, face, larynx, and voice may correspond to the male 
type. In false hermaphrodites the l)ody characteristics do not always 
cori^e.spond to the true nature of the sexual glands: a male may resem- 
ble a female, and vicr rrrsa. 



HERMAPHRODISM. 



52T 



The followii),q- chief types of hermaphrodism may be distiiiguislied: 

1. Hermaphrodismus verus or androgynes. — 1. Hermaphrodismus 
verus bilateral is, or double -sided hermaphrodism, is characterized by the 
presence on both sides of both ovary and testis, or the presence ou 
both sides of an organ containing both ovarian and testicular tissue. 
Heppner asserts that in a nine months' old child, having hermaphroditic 
external genitals, with vagina, uterus, and tubes, both ovary and testis 
were found in the broad ligament ; epididymis and vas deferens were 
wanting. 

2. Hermaphrodismm verus unilateralis, or one-sided hermai)hrodism, is 
that condition in which upon one side there exists but one sexual gland, 
while on the other both testis and ovary are resent. Salen has reported 
a case of a woman of forty-three years of age, who had menstruated since 
her seventeenth year, in whom there was found uj^on the right side (cas- 
tration on account of uterine myoma) a hermaphroditic gland, the 




Fig. 397.— Hermaphrodismus verus lateralis. (After Obolonsky.) a. Urethra : 7>, prostate ; c, colliculus 
seminalis; d, hymen; e, canalis uro^enitalis ; /, bladder; g, vagina; h, uterus; hi, left uterine horn; i, 
left tube; infundibulum of left tube; /c, left ovary; Z, ligamentum ovarii; m, ligamentum teres sin- 
istrum; ?(, right tube ; o, right testicle ; jj, epididymis ; q, right vas deferens : ?\ ligamentum teres dextrum. 
About one-haif natural size. (Specimen in the collection of the Pathological Institute of the derman Uni- 
versity in Prague.) 

nature of which was confirmed by accurate microscopical examination. 
The ovarian portion of the gland was typically develojDed ; the epithe- 
lium of the seminiferous tubules of the testicular portion consisted of 
follicular cells and cells of Sertoli, but lacked spermatogonia and seminal 
cells. Blacker and Lawrence have also described a case of hermaphro- 
ditic gland occurring in a child still-born at eight and a half months. 

3. Hermaphrodismus verus lateralis is that condition in which there is 
an ovary on one side and a testis on the other. It has been many times 
observed in man (Eudolph, Stark, Berthold, Barkow, H. Meyers, Klebs, 
Messner, and others), though in the majority of cases no careful micro- 
scopical examination was made, and when carried out, ovaiian tissue 
could not with certainty be demonstrated. Several years ago Obolonsky 
reported a case (a twelve-year-old girl) from the collection of the German 



528 



DISTURBANCES OF DEVELOPMENT. 



University in Prague, in Avbich the histological examination showed on 
the right side a testicle (Fig. 397, o), and on the left side an ovary (k), 
but it is to be noted that ova were not seen in the latter. The right 
broad ligament contained a testis (o), an epididymis (^), a vas deferens 
(g), a rudimentary tube {n), a round ligament (r) ; the left broad liga- 
ment, on the other hand, contained an ovary {k), with an ovarian liga- 
ment (/), and a well-developed tube (i). Moreover, a uterus (h)y 
vagina {g), and also a prostate (&) were present. According to the re- 
ported observations, the corresiDonding sexual passages may be wholly or 
in part wanting. The external genitals are malformed, and combine 
structures belonging to both sexes. 

11. Hermaphrodismus spurius, or pseudohermaphrodismus, is 
characterized by a bisexual development of the sexual i^assages and ex- 
ternal sexual organs in association with a unisexual development of the 

essential sexual gland. The most 
pronounced cases occur in males, 
who, in addition to their proper 
sexual organs, possess a more or 
less well -developed vagina, uterus, 
and tubes. It is much more 
rare to find in females a develop- 
ment of a portion of the Wolffian 
duct. 

In male false hermaphrodites 
the external genitals are frequent- 
ly malformed and approach the 
female type, while in female false 
hermaphrodites the external geni- 
tals resemble those of the male 
(Fig. 398). 

The resemblance of the" male 
external genitals to those of the 
female is brought about by a 
stunting of the penis and a total or 
partial failure of the sexual fur- 
row in the penis to close (hyi:)OS- 
padias), so that the two halves of 
the scrotum are separated, leaving a depression beneath the root of the 
penis, which represents the remains of the sinus urogenitalis. The scrotal 
halves come, therefore, to resemble the labia niajora, particularly in the 
case of non-descent of the testicles. The external genitals of the female 
approach in appearance those of the male through the development of 
the clitoris into a sort of penis (Fig. 398, a), while the vaginal opening 
is narrowed or closed through the union of the labia. The vagina and 
urethra have a common opening, or open separately beneath the penis- 
like clitoris. 

The atypical development of the external genitals may or may not 
be associated with malformations of the sexual passages; and is, there- 
fore, not dependent upon malformations in other portions of the sexual 
apparatus. 

1. Pseudohermaphrodismus mascuUnus occurs in three varieties: 
First, pseudohermaphrodismus masctdinus intenius, in which condition 
the external genitals are of the male type, and the prostate is developed, 
but is usually pierced at the colliculus seminalis by a canal opening into 




Fig. 398.— External genitals of a female false her- 
mapbrodlte, with stenosis of the vaginal orifice, o. 
Penis-like clitoris ; labia majora. 



HERMAPHRODISM. 



529 



the iiretlira, the former being contiuiied above into a rudimentary or 
more or less well -developed vagina, often also into a more or less well- 
formed uterus, and even tubes. The male organs may be well developed 
or more or less malformed. 

Second, pseudohermapkrodis^nus mascuUnus completus, or externus et in- 
ternus, in which form the vagina, uterus, and tubes are present in a state of 
rudimentary or more or less complete development, while the external 
genitals resemble more or less completely the female tyj^e. The penis 
presents the condition of hyj)OSi)adias and resembles the clitoris ; beneath 
it lies a furrow at whose posterior end there is usually an orifice leading 
into a short vestibule which divides at once into a urethra and a vagina. 
Sometimes the vagina and vestibule are separate. In rare cases the ex- 
ternal genitals appear normal, but the penis contains a double canal, the 
upper one representing the urethra, the other the sexual passage. In 
the case of a more marked development of the ducts of Miiller the vasa 
deferentia are frequently defective, and the seminal vesicles are some- 
times wanting. 

Third, pseudohermapTirodismus mascuUnus externus, in which only the 
external genitals depart from the male type, and resemble more or less 
closely the female. As in these cases the bodily habitus often simulates 
that of the female, the true sex of the individual may easily be mis- 
taken. 

2. Fseudoliermaphrodismus feminimis also occurs in three similar varie- 
ties, but is of much rarer occurrence. 

In pseudoliermaphrodismus femininus internus rudiments of the Wolffian 
ducts, lying in the broad ligament or in the uterovaginal wall, and some- 
times extending to the clitoris, are found in association with well-devel- 
oped external genitals. 

Fseudoliermaphi odismus feniininits externus is characterized by external 
genitalia resembling those of the male (Fig. 398). 

Fseudohermaphrodismus femininus externus et internus, in which the ex- 
ternal genitals resemble those of the male and there is a persistence of 
parts of the Wolffian ducts, is very rare. Of the internal male genitalia, 
there was found in one case a prostate, and in another case a prostate 
pierced by the vagina, an ejaculatory duct, and a sac resembling a semi- 
nal vesicle, which oj)ened into the vagina. 

The internal sexual organs develop from the same imditferentiated anlage in both 
males and females. These anlage consist of a sexual gland lying on the medial ante 
rior side of the Wolffian body, and a sexval passage known as the duct of Miiller. The 
latter develops beside the Wolffian duct, and, like it, empties into the lower end of the 
bladder or into the sinus urogenitalis. 

In the male the duct of Midler disappears, only slight traces in the form of the 
uterus masculinus or vesicula prostatica remaining; the primitive sexual gland unites 
with a small part of the Wolffian body, which becomes the head of the epididymis, 
another small portion forming the vasa aberrantia testis (organ of Giraldes), the re- 
mainder disappears,' while the Wolffian duct becomes the vas deferens and vesicula 
seminal is. 

In the female the Wolffian body and its duct disappear, leaving only a trace in the 
form of the gland-tubules known as the parovarium, but remains of the duct are not 
infrequently found preserved in the uterine wall. From the ducts of Midler, which in 
part coalesce at their lower ends, develop the vagina, uterus, and tubes. The extreme 
upper end of the duct of Midler not infrequently persists in the form of a little pedicled 
sac attached to the abdominal end of the tube, tlie hydatid of Morgagni, 

The anlage of the sexual glands appear in the fifth week. In mammalia (probably 
also in man) the}' develop through a localized thickening of the peritoneal epithelium, 
which becomes the germinal epithelium ( Waldeyer), while at the same time the meso- 
derm also proliferates. Whether the seminal tubules arise from peritoneal epithelium 



530 



DISTURBANCES OF DEVELOPMENT. 



{Boraluiupt Eyli), or whether they are derived from an ingrowth of the Wolffian body 
into the testis-anlage ( Wdldeyer), is still an undecided question {Kdlliker). The ova 
arise from germinal epithelium. The environing cells of the Graafian follicle are 
regarded by TF«W67/e/' as also derived from the germinal epithelium; v;\\\\e KoUiker 
believes that they probably arise from the W olffian body. 

The signiiicance of the pedunculated and non-peduncalated hydatids, found in vary- 
ing numbers near the globus major of the epididymis, is not yet determined {Kdlliker). 
The non-pedunculated c^^st known as the hydatid of Morgagni is regarded by Waldeyer 
as a remnant of the duct of MiXller. According to Roth, it may also stand in a close 
relation to the Wolffian body, inasmuch as there is occasionally found a vas aberrans 
of the epididymis communicating with it. 

In the development of the vagina and uterus the ducts of Milller and the Wolffian 
ducts imite at their lower portion to form a rounded quadrangular cord, the genital 
cord. At the end of the second month the ducts of Miiller blend to form a single canal, 
which then develops into the vagina and uterus. This union takes place first near the 
middle of the genital cord. The Wolffian ducts play no role, though remains of these 
are found at birth in the broad ligament (Kdlliker) and in the wall of the uterus (Biegel). 
According to observations of Riedel, remains of the Wolffian duct are found in about a 
third of adult females, in the form of a tube lined by cylindrical epithelium surrounded 
by muscle, or as a muscle-bundle without epithelium, lying anteriorly and to the side 
of the uterus and vagina. 

The external genitals begin to develop, even before the cloaca has separated into 
the intestinal and genito-urinary orifices, by the formation, in the sixth week, of a me- 
dian genital tubercle in front of the cloaca, and further, of two lateral folds, the genital 
folds. Toward the end of the second month the tubercle becomes more prominent, and 
shows on its lower surface a furrow, the genital furrow. In the third month the cloaca 
becomes divided to form the anal and genito-urinary openings. In the male embryo 
the genital tubercle becomes the penis, the glans being recognizable as early as the 
third month. In the fourth month the furrow closes to form a tube; at the same time 
the two genital folds unite to form the scrotum. 

The prepuce is formed in the fourth month. The prostate arises in the third month 
as a thickening of the tissues at the junction of the urethra and the genital cord. The 
glands of the prostate develop in the fourth month from the epithelium of the canal 
and grow out into the surrounding connective tissue. 

In the female embryo the closure of the genital furrow and the genital folds does 
not take place, so that the sinus urogenitalis remains short. The genital eminence 
becomes the clitoris, the folds become the labia majora, and the edges of the genital 
furrow tile labia minora. 



Literature. 

( True and False Hermaphrodism. ) 

Abel: Pseudohermaphrodismus masculinus. Virch. Arch., 126 Bd., 189L 
Arnold, J. : Uterus masculinus. Virch. Arch., 47 Bd., 1869. 
Becker: Ueber Zwitterbildung. Wlirzburger Verb., 1896. 
Benda: Hermaphrodismus. Elrgebn. d. allg. Path., ii., 1897. 

Blacker and Lawrence: Case of True Unilateral Hermaphrodismus with Ovotestis in 

Man. Trans, of the Obstetr. Soc. of London, xxxviii. 
Briihl: Ueber Hermaphrodismus. Inaug. -Diss., Freiburg, 1894. 
CreccMo: Hermaphrodismus fern, extern, et intern. Wien. med. Presse, 1866. 
Debierre: L'hermaphrodisme, Paris, 1891. 

Geoffroy St.-Hilaire: Traite de teratologic zool., Bruxelles, 1857. 
Henricbsen: Pseudohermaphr. mascul. extern, completus. Virch. Arch., 94 Bd., 
1883. 

Heppner: Hermaphrodismus verus. Du Bois-BcA^mond's Arch., 1870; ref. Cbl. f. d. 
med. Wiss., 1871. 

Keibel: Entwickelungsgesch. d. Urogenitalapparatus. Arch. f. Anat., 1896. 
Klebs: Handb. d. pathol. Anat., i., Bd., 2 Abth., Berlin, 1876. 
Kopsch: Hermaphrodismus verus beim Schweine. Anat. Anz., xii., 1896. 
Laurent: Les bisexues, gynecomastes et hermaphrodites, Paris, 1894. 
Lucksch: Hermaphrodismus spur. masc. int. Zeit. f. Heilk., xxi., 1900. 
Marcband: Hermaphrodismus spurius masculinus? Virch. Arch., 92 Bd., 1883. 
Messner: Hermaphrodismus verus. Virch. Arch., 129 Bd., 1892. 
Nagel: Entwickelungefehler weibl. Genitalien. Handb. d. Gyn., i., 1897. 
Nonne: Pseudohermaphrodismus mascul. Jalirb. d. Hamb. Krankenanst., ii., Leipzig, 
1893. 



DOUBLE MONSTERS. 



531 



Obolonsky; Zur pathol. Anat. d. llcrmaphrodisinus homiuis. Zeitsclir. f. Heilk,, ix., 

Putz; Hermaplirodismus venis unilateralis b. Scliweine. Deut. Zeitsclir. f. Tliiermed., 
XV., 1889. 

Raake: Hermaplirodismus spur. masc. int. Wiirzburger Yerh., 1896. (Lit.)- 
Salen; Hermaplirodismus verus unilateralis. Verb. d. Deut. path. Ges., ii., Berlin, 
1900. 

Schmorl; Ein Fall von Hermaphrodismus. \ircb. Arch., 113 Bd., 1888. 
Sieg-enbeek van Heukelom: Tubulitrer und glandularer Hermaplirodismus. Beitr. 

V. Ziegier, xxiii., 1898. 
Stroebe: Pseudohermaphrodismus masc. int. Beitr. v. Ziegier, xxii,, 1897 
Taruffi: L'Ermafrodismo. Mem. della Acc. delle Sc. dell' 1st. di Bologna, 1899 (Lit.). 
Virchow: Wiirzburger Verb. IH. Berl. klin. Woch., 1872; Ges. Abb , Frankfurt, 

I8r)6. 

Wermann: Pseudohermaphrodismus masculinus completus. Vircli. Arch. 104 Bd,, 
1886. 

Winkler: Pseudohermaphrodismus masculinus internus. Inaug. Diss., Zurich, 1893. 
Zweifel: Krankh. d. auss. weibl. Genitalien. Hanbd. d. Frauenkrankh., iii., Stutt- 
gart, 1886. 

5. Double Monsters. 
(a) Chimficcdion of DouNe Monsters. 

§ 144. Twin=formations lying within a single chorion may be divided 
into two large groups : twins completely separated from one another, and 
ticins united by some jwrtion of their bodies. 

Of the twins completely separated from one another there may be 
distinguished two types; one in wliieli hoth tirins are fully deveJoped, and 
one in which one twin is stunted. 

Twins joined together by portions of their bodies may likewise be 
also divided into two groups: twins showing nufonn development and twins 
showing an unequal development. 

According to the situation of the dui:)licated x^ortions of the body, 
there may be distinguished (Foerster) : 

1. Monstra duplicia katadidyma or duplicitas anterioi'. 

2. Monsti'a duplicia anadidyma or duplicitas posterioi-. 

3. Monsti a duplicia anakatadidyma or duplicitas parallela. 

In general, these mav also be convenient! v divided into three classes 
(Taruffi) : 

1. Twins united chiefly by the epigastrium and thorax. 

2. Twins united chiefly by the heads. 

3. Twins united cliiefly by the pelves. 

Ahlfeld divides tlie double monsters into two chief groups, those with 
complete and those wUJi partial doubling of the axial structures. 
In very rare instances triple monsters occur. 

Literature. 

{Double Monsters.) 

Ahlfeld: Die Missbildungen des Menschen, Leipzig. 1880, 1882. 

Foerster: Die Missbildungen des Menschen, Jena, 1865. 

Marchand: Missbildungen. Eulenburg's Realencyklopadie. xv., 1897. 

Taruffi: Suir ordinameuto della teratoiogia. Mem. della R. Acc. delle Scienze dell* 

Istituto di Bologna, v., 1896; vii., 1898. 

See also § 130. 

(/>) The Chief Forms of Double Monsters. 

% 145. Twins separated from each other and lying within a single 
chorion are designated homologous twins. They are always of the same 



532 



DISTURBANCES OP DEVELOPMENT. 



sex, have usually a coninioii placenta, and resemble each other \ ery 
closely. If from any cause one of the twins should die after its body havS 
been developed, it may be pressed flat by the continued growth of its 
fellow, giving rise to the condition known as foetus papyraceus. 

When twins possess a common ])lacenta within whicli the blood- 
vessels have abundant anastomoses, the heai't of the strongei- foetiis 
may control the circulation and thereby cause changes in the direction of 
the blood-stream in the weaker twin. As a result of this the latter suf- 
fers severe disturbances of development, and becomes changed into an 
acardiacus, a monster without a heart, either developing no heart at all or 

only a rudimentary one. In the ma- 
jority of such cases the head also fails- 
to develop {acardiacus acephalus) or re- 
mains rudimentary (acardiacus paracej^h- 
(dus), and likewise there is usually no 
development, or only a rudimentary 
one, of the upper extremities, thorax 
walls, lungs, and liver, while the ab- 
domen, pelvis, and lower extremities 
are more or less perfectly formed (Fig. 





Fig. 399. 



Fig. 400. 



Fig. 399.— Acardiacus acephalus, showing a rudirneniary development of the lower extremities (acardi- 
acus amorphus). 

Fig. 400.— Acardiacus pseudoacormus. (After Barkow.) a. Head; 7>, rudiment of the left upper ex- 
tremity; c, rudimentary intestine ; d, artery ; e, vein. 



399). According to the development of the extremities the following 
varieties may be distinguished: acardiacus paracephalus (or acephahis) 
sympus, monopus, dipus, monohrachius, dibrachius. 

In rarer cases there is no recognizable development of any i^art of tlie 
body, and there is formed an acardiacus amorphus, consisting of a shape- 
less mass covered with skin, usually without any indications of extremi- 
ties, and possessing internally only rudiments of organs. 

Of very rare occurrence is the formation known as an acardiacus 
pseudoacormus (Fig. 400) — that is, a monster in which the head (a) only 
is developed, while the other parts of the body are represented only by 
small rudiments (&, c). 



DOUBLE MONSTERS. 



533 



Literature. 

(Acardiacus.) 
Barkow: Pseudoacormiis, Breslaii, 1854. 

Claudius: Die EntwickeUuig der herzlosen Missgeburten. Kiel, 1859. 
Dareste: Compt. rent, de I'Acad. des sciences, 1865, 1873. 
Heller: Acardiacus amorpli us. Vircli. Arch., 129 Bd., 1890. 

Hirschbrucli : Das Problem der lierzlosen Missgeburten. Inaug.-Diss., Berlin, 1895. 

liOwy: Acardiacus anceps. Prag. med. Woch., 1892. 

Mulder: Ueber eine herzlose Missgeburt. Inaug.-Diss. , Freiburg, 1891. 

Orth: Drei menschl. Missgeburten. Virch. Arch., 54 Bd., 1872. 

Panum: Zur Kenntn. d. phys. Bedeutung d. angeb. Missbildungen. Virch. Arch., 
72 Bd. 

Perls • Lehrb. d. allgem. Pathologic, ii. , Stuttgart, 1879, 1886. 
See also § 147. 

§ 146. Twins equally developed and united to each other occur in 
the f ollowiDg principal types : 

1. Duplicitas anterior {monstra duplieia katadidyma). Anterior du- 
plication with union of posterior portions of the body. 

Pygopagus (Fig. 401). Union of the twins in the region of the 




Fig. 401. Fig. 402. 

Fig. 401.— Pygopagus. (After Marchand.) A, B, The two twins; a, h, separated umbilical cords; c, 
blended umbilical cords ; d, common placenta. There is a single coccyx and sacrum (from the second 
vertebra downward), and the lower end of the medullary canal is single. The two intestinal canals ter- 
minate in one anal opening. Vestibule of vagina single, the remaining portions of the sexual organs double. 

Fig. 403.— Ischiopagus. (After Levy.) 

coccyx or of the sacrum. According as the union is more or less exten- 
sive, the sacrum, coccyx, lower end of the medullary canal, anus, lower 



DISTUKBANXES OF DEVELOPMENT. 



end of rli(^ I^om-^I. and the sexual apparatus are either doubled or ^u-e in 
part >iiigle. 

Ischiopagus ( Fig. 402 ). Uiiiou of the twius in the pelvis, whieh 
therel:)y I'ornis a wide ring, the two sacra being phiced opposite each 
other. The anus, lower end of the buwel. and the sexual ni-gans may 
be single or double, and the number of the lower extremities two to 
four. 

Dicephalus Fig. 4o;V and diprosopus ( Fig. 404). The duplication 

is limited to the u}>per ]iait of the trunk and head, or only to the neck 
and head, or the head alfnie, (ir, finally, only to ])niti()ii> of the head. 
As the external blending increases in extent, there oecur^al.so a blending 




Fig. 403.— Dicepbalus dibracliius diiais. Fig. — niprosopus distoiiius Tetrophthalniui dio- 

Tiis dibrachiiis. 

of the internal organs, the intestine, liver, lungs, heart, spinal cord, 
brain, etc. According to the number of the lower and upper extremi- 
ties there may be distinguished dicephalus td/"ji'i.s. dipus. fdrabycfchiu.s, 
tribrachiii.s, dihrdchius Fig. 408 K When the lit-ad^ have Idended there 
may be distingtiished diprosopvs. ff fmplifh^ilni us. fi'ioplitlKdmus. diophthalmus, 
tetrotus, trlotus. diotu.s. r//.v/o//?'/-s'. mniiosioni ns. tiuhrarltius and dihracJuus *^Fig. 
404). 

The mildest grades of dtiplicitas anterior are represented l)y the rare 
cases of dupJication ofthejaic, mouth, or nose. 

2. Duplicitas posterior (monstra dupJk-ki anadidi/ma). Union of the 
twins at the head and thence farther downward with duplication of the 
posterior parts of the body. 

Craniopagus (Fig. 405)). Union of the twins in the cranial region. 



DOUBLE MONSTERS. 



535 



According to the site of union there may be distinguished o'aiiiojyaf/ns 
parietalis, frontaJiH, occipitalis. When the union is more extensive por- 
tions of the brain ai e also single. 

Cephalothoracopagus or syncephalus (Fig. 
406). Blending of the twins in the region of 
the forehead and face, and in i^art also of the 
abdomen. In the region of the united heads 
there is an anterior and a posterior face (janns, 
Janicejjs). The two faces may be equallj' (^jauus 
si/nnncfros) or unecxually develoi^ed (janus asym- 
/nctroi^), one face being well developed, the 
otlier imperfectly. The internal organs present 
diffeient degrees of blending and union into 
single oi'gans. 

^ , Dipygus. The duplication is limited to the 

i 




FIG. 405. 
Fig. 405.— Craniopagus parietalis. 



Fig. 406. 



Fig. 406.— Cephalothoracopagus or syncephalus, with janus head. Both anterior and posterior faces are 
malformed, and possess but one eye, while the nose is represented by a proboscis-like organ situated above 
the eye. 



lower half of the body and the lower extremities, while the upper 
parts are either wholly single or only partly cleft. The duplication 
of the spinal cord may begin at different heights. According to the 
number of extremities different forms may be distinguished. The 
mildest grades of duplication are confined to the lower end of the spinal 
column, the anus, and the external genitals. 



536 



DISTURBANCES OF DEVELOPMENT. 




8. Duplicitas pa rail el a 

(iiwnstra dupJiciu anakcitadidy- 
iiia). Dux^lication of the ante- 
rior and posterior ends of the 
body with parallel positions of 
the trnnk. 

Thoracopagus (Fig. 407). 
Union of the twins by the 
thorax. According to the site, 
and extent of the union, as well 
as the number of extremities 
present, there may be distin- 
guished different forms, partic- 
ularly the following: xiplwpagus 
(union at the xiphoid process), 
sternopagus (union at the ster- 
num), thoracopafius tetrabrachius, 
tribrachius. dibi'achius, tet)-apus, 
tripus, aud dijius. When por- 
tions of the faces have blended 
there results a prosopothoraco- 
pagus. Blending and union of 
the internal organs into single 
organs vary with the degree of 
external blending. The heart 
may be double or single, in 
the latter case malformed. 
Thoracopagus is relatively fre- 
quent. 

Rachipagus Blending of the twins in the region of the spinal col- 
umn is very rare. 

Literature. 

{Double Monsters.) 

Ahlfeld: Die MissbiJdungen des Menschen, Leipzig, 1880. 

Barkow: MoDstra auimaHimi duplicia per auatomen indagata, Lipsia-, 1828. 

Burckhard: Z^vei Doppelmissbildimgen. Zeit. f. Gebh.."xl., 1898. 

Lochte: Doppelmissbildimg. Beitr. v. Ziegler. xvi.. 1894. 

Marchand: Pygopagus. Beitr. v. Ziegler, xvii.. 1895. 

Martinotti e Sperino: Diprosopus tetroplitlialmus. Internat. Mouatssclir. f. An., v., 
1888. 

Rtihe: Janiceps asymmetros. Inaug.-Diss., Marburg. 1895. 
Schaefer: Ueber einen Dicepbaliis. Beitr. v. Ziegler, xxvii.. 1900. 
Sieg-enbeek van Heukelom: Monstr. double. Kec. de trav. du Lab. Boerhaave, i. , 
1899. 

Taruffi: Syncephalus dilecaiuis (Verdopp v. Penis, Scrotum, Anus). Mem. B. Acc. 

Bologna, Ix., 1889: Feto umano con due mandibole. lb., ii., 1895. 
Virchow: Pygopagus. Berl. klin. Wocb., 1873. 

See also ^§ 132 and 117. 

§ 147. Twins joined together but unequally developed may occur 
in any of the double forms described in § 146. If the development of 
one of the twins remains rudimentary and if its heart does not develop, 
its nourishment can come only through its well-developed fellow. The 
better developed of the two is then known as the autosite, the other as 
the parasite. If the parasite is of only very rudimentary development, 
it may be classed with the bigeminal teratomata (cf. §§ 128 and 129). 



Fig. iOT.— Thoracopaffus rribrachiu.s tripus. The hand 
of the Third arm. common to both halves, possesses 
two doi-sal surfaces, and the laterally distorted flnarers 
possess nails on both sides. The common third foot^has 
eiffht toes. 



DOUBLE MONSTERS. 



537 



At the posterior ends of the body there may occur a rudimentary para- 
sitic double monstrosity in the form of an iyicrease in the number of the ex- 
tremities, apolymelos (Figs. 408, 409). 
The supernumerary extremities may 
be one or two in number, and more 
or less well developed. The malfor- 





Fig. 408.— Polymelos. (After Lanoereaux.) 



Fig. 409.- Polymelos. (After Lieschiug.) 





Fig. 410. 



Fig. 411. 



Fig. 410.— Bigermlnal teratoma of the coccygeal region (pygopagus parasiticus), a, b, c. Extremities 
lying in a sac formed by the skin of the autosite. 

Fig. 411.— Thoracopagus parasiticus (polymelia). Three legs spring from the pelvis ; one of them has 
a double foot. Two upper extremities project from the anterior chest-wall. 

30 



538 



DISTURBANCES OF DEVELOPMENT. 



mation may be regarded as a dlpuf/uH parasiticus. Further, there not 
infreqiieiitly occur coccygeal teraioniata iu which the presence of rudimen- 
tary extremities (Fig. 410, a, b, c) or of various body elements leaves no 
doubt that the tumor-like formation covered by the skin of the autoslte 
is to be regarded as a double monster, a rudimentary pygopagm, or else as 
a dipygus parasiticus. Such a parasite is designated as an epipygus. 

Supernumerary extremities (Fig. 411) may also be found upon the 
trunk, or there may occur a headless trunk with extremities (Fig. 412), or a 
rudimentary thorax without extremities, or, finally, teratomata which may be 
interpreted as thoracopagus 2)arasiticus and 




Fk;. 412. FiCr. 413. 

Fig. 412.— Thoracopagus parasiticus. (After Schenk von Grafenberg.) Parasite attached to chest of 
autosite. 

Fi«. 413.— Eplgnathus. (After Lancereaux.) 

or within the abdominal or thoracic cavities of the autosite, gives rise 
to the condition know^n as inclusio fwtalis suhcutanea, or ahdominalis, or 
mediastincdis. The abdominal inclusion is also designated engastrius. 

In the region of the head rudimentary twin-formations appear most 
often in the mouth cavity, forming usually an amorphous mass, firmly 
attached to the base of the skull, and consisting of skin, connective tis- 
sue, cartilage, bone, brain -tissut^, teeth, intestinal elements and muscle, 
and rarely developed extremities. Such malformations are included 
under the designation of epignathus (Fig. 413). 

On other parts of the head rudimentary twin-formations or bigemi- 
nal teratomata are very rare (cf. §§ 128, 129). 

Literature. 

(Z^nequal Double Jlonsters.) 
Bdhm: Sacralteratoni. Berl. kiln. Woch., 1872. 

Braune: Die Doppelbildungen u. angeb. GeschwlUste d. Kreuzbeingegend, Leipzig, 
1862. 

Breslau u. Rindfleisch. : Foetus in foetu. Yircli. Arch., 30 Bd., 1864. 
Calbet: Contrib. a I'et. des tumeurs congen. d'origine parasitaire de la region sacro- 
coccygienne, Paris, 1893. 



DOUBLE MONSTERS. 



539 



Foederl: Dipyirns parasiticus, Laiigenbeck's Arch., 58 Bd., 1899. 
Freyer: Krcuzbeiiigesclnvulst. Yiicli. Arch., 58 Bd., 1873. 
Gross: Les iiionstres doubles jiarasitaires. Nancy, 1877. 

Hennig: Cong-eiiitalc cchte Sacraltnnioren. Beitr. v. Ziegler, xxviii., 1900. 
Israel: Eiu Fall vou Verdoppekmg dcr 1. Uuterkieferhalfte. Inaug.-Diss., Berlin, 
1867. 

Moussaud: Des iucliisioiis foetales. These de Paris, 1861. 

Otto: Ziisammenstelhiiig d. bestbesclirieb. Falle v. Epignathus. Arch. f. Gyn., viii. 
Schwarz: Beitr. z. Geschichte d. Foetus in foetu, Marburg, 1860. 
Tarufa: Caso d'engastro amorfo extraperitoneale. Mem. R. Acc. Bologna, iii., 1893. 
Wright and Wylie: Included Fa'tus. Brit. Med. Jouru., ii., 1900. 
See also §§ 128, 129, 132, and 144. 



CHAPTER X. 



The Parasitic Fission=fungi and the Diseases Caused 

by Them. 

I. General Considerations Regarding the Schizomycetes or Fission^ 

fungi. 

1. General Moephology and Biology of the Fissiox-fungl 

§ 148. The Schizomycetes or fission=fungi, often also designated 
collectively as bacteria, belong to the j^/'o/oj^/^z/fes— that is, to the smallest^ 
sinij^lest forms of plant-life. Many of them are so small that they stand 
upon the very border-line of invisibility even with the use of the highest- 
power objectives and eye-pieces. AYhen occurring in animal tissues, it 
is often very difficult to distinguish them from the products of cell-dis- 
integration; and often this can be accomplished only through the em- 
ployment of specific reagents or staining -methods, and occasionally only 
through culture experiments. 

The SchizoDU/cetes throughout are non-cliloropliyUaceous. unicelhdar or- 
ganisms, but as a result of their growth and multiplication they often 
form colonies made u^) of numerous cells. 

The form and character of the single cells, as well as their manner of 
growth, division, and multiplication, vary greatly, and at present these 
differences are used as a basis for the classification of bacteria. In the 
first class are placed the Cocci, often designated as Micrococci or as Sphcero- 
hacteria (Cohn), that form of bacteria which constantly occurs in the 
form of splierical or ovaJ cells. According to the groui^ing of the cells 
during their division, there may be distinguished six forms of cocci: 
doiihle-cocci or Dip>lococci, chain -cocci or Streptococci, clustered cocci or StajyJi- 
yJococci, tahJet-cocci or Merismopedia, pac'ket-sliax^ed cocci or Sarcince, and 
tube-cocci or Ascococci. 

The second class constitutes the Bacilli (rod-shaped bacteria) which 
formerly were divided by Cohn into Jlicrobacteria and Desniobacteria, ac- 
cording to the length of the rods. These may also be designated as sliort 
rods and long rods. In association with the designation bacillus many 
authors use the term Clostridium, particularly for bacilli which during 
spore-formation assume spindle or club shapes. Long threads are often 
also called Leptothrix. 

To the third class belong the Spirilla (screw-shaped bacteria). 
Screw-shaped forms with short, wide turns are known as Spirilla, those 
with drawn-out turns as Vibrios, those with a long, closely wound screw as 
Spirochcetes. According to their length the spirilla may also be divided 
into sJwrt screws and long screws. 

All of the bacteria thus far referred to occur either in one single form 
or in a very limited cycle of forms of growth, and they may therefore be 
grouped together as monomorphous or oligomorphous bacteria. Cohn, 

540 



GENERAL MORPHOLOGY AND BIOLOGY. 



5.1:1 



to whom we are indebted for the fundamental investigations regard- 
ing bacteria, united under the term bacteria only the oligomorphic 
forms. 

Many writers, however, classify also as bacteria those organisms which 
during their development pass through a whole series of forms : spherical 
cells, as well as rods and simple and branching threads. These may be 
collected into a second grou]3— the polymorphous bacteria — to which 
belong in particular the fungi known as Sfreptothrijc, CJadothrix, Beg- 
giatoa, and Crenothrix. Other authors (Lehmann, ^seumann, Levy, Lu- 
barsch) classify these forms with the Myphomycetes or regard them as 
transition forms between the latter and the Schizomi/cetes. 

All of the Schizomycetes consist of a plasmatic cell=contents and a 
celNmembrane, both of which, according to ^N'encki, consist essentially 
of au albuminoid body, mycoprotein, which varies with the species. 
Many bacilli contain fat within their cell-bodies, at times so abundantly 
that it may be demonstrated by staining Avith Sudan III. Some of 
these bacteria (tubercle-bacillus, lepra-bacillus, and actinomyces) show 
the presence of fat both when growing in living tissues and when culti- 
vated upou artificial media; others (staphylococcus aureus, anthrax- 
bacillus, bacillus of glanders) show the presence of fat only when growu 
upon certain media (Sata). According to A. Fischer the cell-contents 
consist of a ^protoplasmic tube without a nucleus, but containing a cen- 
tral collection of fluid. Biitschli, Schottelius, and others regard the cen- 
tral bodies, recognizable in certain bacteria, as nuclei. According to 
investigations by Ziemann, Zettnow, and Feinberg, it is possible by 
staining with a mixture of methylene -blue and eosin (Romanowski -stain) 
to demonstrate in the cells of the majority of bacteria a nuclear sub- 
stance," or chromatin " (Ziemann, Zettnow), or nucleus" (Feinberg) 
— that is, bodies of varj ing size lying within the bacteria, wliich stain red 
as do the nuclei of malarial plasmodia (Eomanowski) or of other i^roto- 
zoa or of tissue-cells, while the protoplasm takes a blue color. Accord- 
ing to I^aegeli, Zo^^f , and others, many schizomycetes possess a membrane 
of cellulose or of a carbohydrate closely related to cellulose. In many 
forms of bacteria the membrane swells under certain conditions of 
growth, and forms a capsule having a hyaline appearance. Certain bac- 
teria {red suJphur-Meteria) contain coloring matter within their cell- 
bodies, others {BaciUus (onylobaetei; S2)i) iUum amijlofevum) give at certain 
stages of their growth a marked reaction witli iodine. 

In all forms of bacteria, with the exception of the cocci, there have 
been observed swarming movements wliicli are bix^ught about by means 
of fine thread-like flagella attached singly at the ends or scattered over 
the entire bacterial cell. In addition there also occur slow oscillatory 
or gliding and creeping movements which are dependent upon the con- 
tractile and flexible qualities of the plasma. Both forms of motion occur 
only under certain conditions of nutrition and growth, and only in cer- 
tain species. 

riultiplication of bacteria takes place through a transverse division 

of cells which have iDreviously become elongated. In some forms divi- 
sion can also take place in two or even three dimensions. After division 
the cells separate immediately or remain for a time attached to each 
other. When the cells remain attached after dividing transversely, 
threads are formed (Streptococcus, Leptothrix) ; after dividing both trans- 
versely and longitudinally, flat, tablet=like colonies (Merismopedia) ; 
after dividing in all three dimensions, colonies resembling a solid body 



642 



THE PARASITIC FISSION-FUNGI. 



(Sarcina) are produced. Long tlireads may become segmented into' 
shorter pieces. 

According to the investigations of Bnclnier, Longard, and Eiedlin, the 
period of reproduction — that is, the time from one cell -division to the 
next — is, in the case of the cholera-spirillum under favoi'able conditions 
of nutrition, about fifteen to forty miinites. 

If resting bacterial cells, as the result of a constantly progressing re- 
X^roduction or through the accumulation of neighboring cells, hesLj) them- 
selves anywhere in great masses, there are often formed jelly-like colo- 
nies, which are called zoogloea. The jelly-like substance is formed from 
the membranes of the bacteria and, according to Kencki, consists of 
niycoprotein. The jelly masses may assume the most varied form, and 
occasionally reach a large size, so that the clumps, or lobulated masses, 
or strands may attain a diameter of one to three or more centimetres. 

Under certain conditions many of the bacteria form spores. These 
are cells which are distinguished by the fact that they j'emain alive under 
conditions in which the ordinary forms of vegetation die; and, when 
brought into fresh nutrient solutions, are able to produce a new gener- 
ation. Spo 'e-formationi^ mo^t ivQqv\Qwi\j endogenous — that is, the spore 
arises inside the cells (particularly in bacilli), and is develoi^ed out of 
the cell-protoplasm, in which there appears a small granule which grows 
into an obloiig or round, highly refractive, shai'ply-contoured body 
always remaining smaller than the mother-cell. After the death of the 
latter the spore is set free. Arthrogenous spore-formation, as observed in 
micrococci, is said to occur through the direct assumption of spore-quali- 
ties by individual members of a colony or of a series of generations, which 
at the same time remain externallj^ unaltered or take on other morj^ho- 
logical peculiarities. 

In old cultures bacteria nearly always show degeneration=forms, 
which are swollen and distorted, and stain poorly and irregularly. 

As non-chlorophj^llaceous plants, the schizomycetes are restricted in 
their nutrition entirely to ready-formed organic substances which are 
soluble in water, and which are also supplied to them in an abundance 
of water. In addition they need also various mineral substances, 
especially sulphur, phosphorus, potassium or rubidium, or caesium and 
calcium (or magnesium, barium, or strontium). 

The carbon necessary to their growth they are able to take from most 
of the carbon compounds which are soluble in water. They can also 
derive their carbon from dilute solutions of substances which in greater 
concentration are injurious to them — as, for example, from benzoic acid, 
alcohol, salicylic acid, phenol, etc. 

Their nitrogen is derived from alhuminous matter ; further, from those 
compounds designated as amins (methyl-, ethyl-, propylamin), amido-acids 
(asparagin, leucin) and amides (oxamide, urea), as well from the am- 
monia-saJts and in part also from nitrates. The albuminates, previous to 
their assimilation, are changed into peptone by means of a ferment given 
off from the bacteria. Free nitrogen cannot be assimilated as such. 
I^^itrogenous and non-nitrogenous compounds are not only assimilable as 
such, but also in combination. The fission -fungi are able to take nitro- 
gen from ammonia and iiitric acid only in the presence of organic carbon 
compounds. 

Sulphur, according to Kaegeli, is essential to the schizomycetes, and 
they take it from sulphates, sulphites, and hyi:)osulphites. The other 
mineral substances mentioned above are derived from various salts. If in 



GENERAL MORPHOLOGY AND BIOLOGY. 



the case of an abiiiidaiice of uutrieiit matei'ial there is too little water 
present, all further growth ceases; yet many of the tission -fungi are able 
to dispense with water temporarily. Spores suffer little from drying. 

Some of the fission-fungi are either chietly or wholly i-estricted for 
their food-supply to dead organisms or to solutions of organic matter, 
and are, therefore, classed as saprophytes ; others are able to take their 
nutrition also from living animals or plants, and live as parasites. 

If bacteria get into water which contains no food-material, many of 
them die in time. The spores survive the longest. 

Free oxygen is necessary for the development of many bacteria; 
others can dispense with it as long as they are under favorable conditions 
of nutrition in other respects ; others develop only in the absence of oxy- 
gen. The first are designated obligate aerobes, the second facidtative 
anaerobes, the third obligate anaerobes. 

The facultative anaerobes i3roduce in part fermentation through their 
multiplication in the absence of oxygen ; but according to the investiga- 
tions of Fliigge and Liborius, the phenomena of fermentation appear 
often to be absent. The pathogenic bacteria are, according to Liborius, 
facultative or obligate anaerobes. 

Carbon dioxide has no influence upon the development of many 
bacteria, as, for example, upon the typhoid- bacillus and Friedlander's 
pneumobacillus. Upon others, on the contrary, it has an inhibitory 
action, as, for examx)le, upon Bacillus indicus, Proteus vulgaris. Bacillus 
phosphor escens, the bacilli of anthrax and cholera, the pus-cocci, and 
others (C. Frankel). The bacilli of anthrax, Asiatic cholera, and of 
rabbit septicaemia die out in a few hours in artificial Seltzer water, but 
anthrax-spores remain alive in it indefinitely (Hochstetter). 

Intense light has an injurious or destructive influence upon the de- 
velopment of many forms of bacteria, and it is therefore possible to dis- 
infect by means of strong light water which is infected (Buchner). The 
virulence of the bacillus of anthrax may be lessened by exposure to sun- 
light (Arnold, Gaillard). When exposed to the direct rays of the sun 
anthrax bacilli die in twenty-four to thirty hours, the spores survive as 
long as six to eight weeks (Arloing, Duclaux). According to Geisler 
the green, violet, and ultra-violet raj s are particularly active. Accord- 
ing to Kieder bacteria may be destroyed by the Eoentgen-rays. 

According to Xaegeli, Hauser, Buchner, Zojjf, and others, different 
conditions of nutrition act in modifying the form and dimensions of the fission- 
fungi. Thus, for example, bacilli cultivated in different nutrient solu- 
tions assume different lengths and thicknesses. Further, many varieties 
form in one medium spherical cells and short rods, while in another, on 
the other hand, they form long threads (Zopf). Finally, the physiological 
properties may also change with the different conditions of nutrition. 

The temperature of the surrounding medium acts in general upon the 
bacteria in such a way that when it falls the life-processes of the organ- 
isms become weaker and slower, and finally cease entirely, whereas with 
an elevation of the temperature they rise to a certain maximum, and at 
a slight increase above this suddenly cease; still higher temperatures 
kill the fungi. The maximum of permissible temperature lies at a dif- 
ferent height for different fungi, and is in part dependent also upon the 
character of the nutrient substance. There are forms of bacteria which 
grow well at a temperature of 55° C. or higher. 

A low temperature checks development in all varieties ; they fall into 
a state of immobility, but do not die even at great degiees of cold. The 



544 



THE PARASITIC FISSION-FUNGI. 



immobility due to cold occurs at different temperatures with different 
varieties. The most favorable temperature for development lies between 
30° and 40° C. for the anthrax bacillus ; at temperatures above 44° and 
below 15° C. its development ceases. Many bacilli form spores only at 
high temperatures. 

Boiling water and steam at 100° C. kill all bacteria and bacterial 
spores if allowed to act for some time. In dry air bacteria and their 
spores withstand higher temperatures, so that a temperature of 140° C. 
for three hours is necessary to kill the latter. Many bacteria are killed 
at a temperature of 60° to 70° C, provided it is kept up for a very long 
time. 

Anthrax-spores die in boiling water in two hours, in confined steam 
in ten minutes. The action of steam at 105° C. for ten minutes kills all 
spores. Live steam kills all spores in ten to fifteen minutes, and pene- 
trates very well into the objects to be disinfected (Koch, Gaffky, Loffler). 

If fission-fungi find themselves in a suitable medium, their multiplica- 
tion can still be brought to a standstill, since the fluid may contain sub- 
stances which hinder the growth of the bacteria or even kill them. 
This effect is produced by many substances (sublimate, lysol, carbolic 
acid, iodine, formaldehj^de, etc.) — even in comi)aratively great dilution. 
Other substances act injurioush^upon the bacteria only when in stronger 
concentration. The point at which the multiiDlication is hindered is 
always reached at a much greater dilution than that at which the bacteria 
are killed. Spores are much more resistant than the vegetative forms. 

Many bacteria are sensitive to acids, so that even a slight degree 
of acidity hinders their growth (for example, anthrax bacilli and the 
Frankel-\Yeichselbaum pneumococcus). Others are able to grow with a 
moderate amount of acid in the nutrient fluid. As a general rule they 
are especially sensitive to mineral acids, but the presence of a large 
amount of citric, butyric, acetic, and lactic acids hinders also their mul- 
tiplication. In this connection belongs the fact that the products of 
decomposition caused by the fermentative action of the fungi are at a 
certain degree of concentration harmful to the development of the fun- 
gus, and finally stop its growth entirely. Thus, for example, in butyric - 
acid and lactic -acid fermentation the amount of butyric or lactic acid 
gradually formed finally checks the multiplication of the fungus. A 
similar result occurs in the bacterial xDutrefaction of albumin, since the 
XDroducts of the same, such as phenol, indol, skatol, phenylacetic acid, 
phenylpropionic acid, etc., hinder the further development of the bac- 
teria. To alkalies the fission-fungi are less sensitive, and many can 
bear a rather high degree of alkalinity in the nutrient fluid, but there 
also exist forms which do not thrive in alkaline fluids (acetic-acid 
fungus). 

The growth and multiplication of bacteria also cease in the presence 
of a sui^erabundance of nutrient material — ^that is, in the case of insuf- 
ficient amount of water. The fact that fruits preserved in sugar do not 
ferment and that salted and dried meats do not putrefy depends upon 
this fact. Food-stuff's can also be preserved through the removal of 
water and by the addition of substances which are dissolved in the 
tissue-fluids and in this way increase the proportion of the same in solid 
contents. The limit at which the fission-fungi and yeast-fungi cease to 
develoi) is reached at a much higher degree of humidity than for the 
moulds. 

According to the investigations of Pfeffer and Ali-Cohen many motile 



GENERAL MORPHOLOGY AND BIOLOGY. 



545 



bacteria show chemotactic properties — that is, they are attracted or 
repelled by certain chemical substances dissolved in water. Bacteria 
swimming about in fluids collect, therefore, at places where there are 
chemiccil substances which attract. For example, typhoid -bacilli and 
cholera-spirilla are attracted by potato-juice (Ali-Oohen). Potassium 
salts, peptone, and dextrin likewise attract, but the individual forms of 
bacteria behave very differently toward these substances. Free acids, 
alkalies, and alcohol have a repelling action. 

If a nutrient fluid contains other lower fungi besides the bacteria 
there often takes place a competition between the different micro=or= 
ganisms ; and fission-fungi, yeasts, and moulds may crowd one another 
out. Likewise a reciprocal crowding between the bacteria themselves 
may occur. For example, cocci may be crowded out and destroyed by 
bacilli, or one form of bacillus by another. This would happen when 
either the composition or the temperature of the nutrient medium is 
more favorable to one form than to the other; or also when one form of 
bacteria produces products which act injuriously upon the other, or 
when one form grows more rapidly than the other, and thereby deprives 
its competitor of the necessary food-supply. 

According to investigations by Pasteur, Emmerich, Bouchard, Wood- 
head, Blagovestchensky, and others, the antagonism between many forms 
of bacteria is shown also in inoculation experiments on animals. By 
simultaneous inoculation with difl'erent bacteria the development of a 
pathogenic bacterium in the body of a susceptible animal may be hin- 
dered. For example, the development of anthrax bacilli may be hin- 
dered by simultaneous inoculation with erysipelas -cocci (Emmerich) or 
with the BaciUus pyocymieus (Bouchard). 

Babes and Ernst, by means of especial staining methods with Loffler's methylene- 
blue, hcematoxylin, and Plainer s nuclear black, have demonstrated the presence of 
granules tiyitJiin different forms of bacteria, which according to their behavior probably 
stand in some relation to the processes of division and spore-formation. Ernst desig- 
nated the appearances seen by him as sporogenous granules, since he was able in certain 
bacteria to demonstrate their transition into spores ; he is inclined to regard them as of 
the nature of cell-nuclei, a view which Biitscldi also favors, Bunge regards the gran- 
ules described by Ernst as cell-granules which have nothing to do with spore-forma- 
tion, and describes other granules, which stain with Ldfflers methjdene-blue, as the 
forerunners of spores. Marx and WoitJie regard the Babes-Ernst granules as not being 
nuclei in the ordinary sense of the word, but as representing products of the maximal 
condensation of the euchromatic substance of the cells, which are a sign of the highest 
intensity of vitality on the part of the cell. Wagner, on the contrary, holds that cer- 
tain bodies, which he has observed in typhoid- a^jd colon-bacilli, are nuclei. 

According to JS'aA-anisM, the spores form (in anthrax- and hay-bacilli) by a concen- 
tration of the chromophile substance about the nucleus, while the remaining portion of 
the protoplasm becomes clear; a membrane is then formed about the chromatin body, 
it takes on a fat-like shine, and loses its power to take stains (methylene-blue BB). 

The Romanowski stain is a mixture of methylene-blue and eosin, whereby a red 
dye contained in methylene-blue {Eosin, Berl. klin. WocJien., 1899; JSoeld, Cbl. f. 
Bakt., 1899) is precipitated. Zettnow's formula is as follows; 50 c.c. of a one-per-cent. 
solution of methylene-blue (Hochst) is mixed with 3-4 c.c. of a five-per-cent. soda solu- 
tion. To 2 c.c. there is added drop \)y drop while shaking 1 c.c. of a one-per-cent. 
solution of eosin (Hochst BA). Stain on cover-glass for five minutes. Examine in 
water. 



516 



THE PARASITIC FISSION-FUNGI. 



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548 



THE PARASITIC FISSION-FUNGI. 



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Zettnow: Romanowski's Farbung bei Bakterien. Zeitsclir. f. Hyg., 30 Bd., 1899; 

Deut. med. Woch., 1900. 
Ziemann: Ueber Malaria u. andere Blutparasiten, 1898. 

§ 149. The growth and multiplication of the fission=fungi give 
rise always to chemical transformations of the nutrient material, 

which are brought about iu part through the influence of ferments pro- 
duced by the hacteria, and in part directly through the laetahoUc processes 
occurring within the hacterial cells themselves. 

Among the ferments or enzymes are to be mentioned first the prote- 
olytic or alhumin-dissoJcing enzymes (haeteriotrypsins) which bring about a 
solution of the albuminous bodies and cause the disintegration of the 
peptone-molecule. Further, bacteria give rise to diastatie ferments which 
convert starch into sugar, also to inverting ferments which transform cane- 
sugar (disaccharid) into grape-sugar (monosaccharid). 

The chemical results of bacterial metabolism, which are brought 
about by the vital activities of the fission-fungi aided by the enzymes 
produced by them, consist in the first place of a decomposition of com- 
plex organic comiDounds. By many authors all these processes are desig- 
nated as fermentations, while others (Lehmann) speak of fermentation 
only when a fission-fungus breaks down a given food-material with espe- 
cial ease, thereby giving rise to one or more especial products in marked 
quantity, in association with or in place of its other metabolic products. 
Other authors still narrow the term fermentation to the decomposition of 
carbohydrates. 

In the decompositions caused by the fission=fungi very different 
products are formed, which vary according to the composition of the 
nutrient material and the character of the fission-fungus. For the pro- 
duction of fermentation a proper fermentable material is necessary. 
Many fungi are able to cause fermentation in the presence as well as in 
the absence of oxygen, while to some of them a lack of oxygen is neces- 
sary. 

Among the products of bacteria of especial importance to the physi- 
cian are those which have a poisonous action and cause tissue=changes, 

to which belong particularly those substances which are described as 
ptonia'ins, toxins, and toxaJl)umins. 

The ptomains are basic, crystallizable, nitrogenous jiroducts of the 
bacterial decomposition of albumin 3 they are also known as putrefactive 



PRODUCTS OF THE VITAL ACTIVITY OF BACTERIA. 



5^9 



alkaloids or cadaveric aJkaJoids. When these disi^lay poisonous properties 
they are chissed with the toxins. The best known are sepsin, putresciu 
(dimethylethylendiamin), cadaverin (peutaniethylendiamin), collidin 
(pyridine derivative), peptotoxin, neiiridin, neurin, cholin, gadinin, and 
substances resembling muscarin. 

The toxalbumins are amorphous poisons, which may be precipitated 
from bouillon cultures containing many bacteria by the same methods 
that cause the precipitation of albumins. They are, therefore, regarded 
by most investigators as albuminons bodies. It should be noted, however, 
that they are, possibly, in part, only bodies which are carried down with 
the precipitated albumin ; and in proof of such a conception speaks the 
fact that the specific poisons of tetanus and diphtheria have been shown 
(Brieger) to be free from albumin. It appears, therefore, more correct 
to designate these specific poisons as toxins. They constitute those 
poisons which determine the special form of intoxication in the various 
infectious diseases. 

Among other decompositions produced by bacteria the following are 
worthy of note: the formation of lactic acid, formic acid, acetic acid, 
propionic acid, butyric acid, often also the formation of alcohol and car- 
bonic acid from sugar; the formation of acids (acetic, butyric, pro- 
pionic, valerianic, succinic, formic, and carbonic) from alcohol and 
organic acids; the formation of indol, skatol, phenol, cresol, pyrocat- 
echin, hydrochinon, hydroparacumaric acid, and paroxyphenylacetic 
acid (von Nencki, Salkowski, Brieger), and finally hydrogen sulphide, 
ammonia, carbonic acid, and water from albumin ; the formation of am- 
monium carbonate from urea ; the transformation of nitrous and nitric 
acids into free nitrogen ; the reduction of nitrates to nitrites and to am- 
monia, etc. Finally, there are also bacteria living in the soil — the nitro- 
bacteria — which are able to form nitrous and nitric acids from ammonia 
( Winogradsky ) . 

Along with the nitrification of nitrogen there occurs simultaneously 
a decomposition of earthy alkali carbonates, as show^n by the fact that 
the nitrobacteria are able in the presence of organic carbon compounds 
to derive /rom the carbonates the carbon necessary to the Maiding- up of the 
cells. There takes place, therefore, through the vital activity of these 
organisms, a synthesis of organic material out of inorganic substances. 

Under the influence of the fission-fungi there are formed bitter, sharp, 
nauseating substances (bitter milk). Further, bacteria occasionally pro- 
duce ^i^mew^s of a red, yellow, green, blue, or violet color. For exam- 
ple, Bacillus prodigiosus produces a blood-red coating upou bread (bleed- 
ing bread) ; bandages and pus take on a bluish-green color as the result 
of the presence of the Bacillus pyocyaneus. In many cultures there is also 
formed a fluorescent coloring matter. 

The phosphorescence not infrequently seen upon decomposing sea-fish 
depends also upon bacterial products of decomposition, as has been 
shown by Pfliiger, and appears when there is an active multiplication of 
the bacteria. 

The first investigations to establish the nature of the processes of putrefaction were 
made by Th. Schwann a.nd Franz Schuhe {Pooggend. Annl., 29 Bd., ref. in Schmidt's 
Jahrh. , 1866), in the middle of the fifties, and upon the results of their experiments 
was based the view that fermentation and decomposition are dependent upon the pres 
ence of very small organisms. Almost at the same time (1857) Cagnard-Latour observed 
the increase of yeast-cells in the course of alcoholic fermentation. The observations 
made by Schwann were later confirmed by Helmholtz. H. Schroeder and von Dusch 



550 



THE PARASITIC FISSION-FUNGI. 



then sliowed that by tilterinii; through cottou-wool the air admitted to a fluid capable 
of fermentation, as well as by the action or higher tempei'atures, the appearance (jf fer- 
mentation may be hindered. 

Since the investigations of Srhir((un, many different hypotheses as to the cause 
of fermentaiion, alcoholic fermentation in particular, have been advanced. Certain 
writers have endeavored to bring these processes into immediate relationsliip with the 
life of the cells causing the fermentation ; others have sought to separate them from the 
latter. According to Liebig, tlie process is due to a molecular movement which an im- 
formed ferment or body in a state of chemical activity — that is, decomposing — imparts 
to other .bodies whose elements are not closely held togetliei-. According to lloppe- 
and Traube{c.i. Ilojype-Seyler, Pfluger's Arch., Bd. xii., 1875; PJiysiologische (JJumle). 
the cells produce certain substances, the so-called unformed ferments, which caus*' 
decomposition by contact action — that is, merely through their presence, without tak- 
ing part chemicall}^ or entering themselves into combination; 

According to Pasteur (cf. Pasteur, Ann. cle cldtn. et de Phys., tome 58, 1860, and 64, 
1862; Gomptes rend, de V Acad, des Sciences, tomes 45, 46, 47, 52, 56, 80; and Dwhitix, 
"Ferments et maladies," Paris, 1882), fermentation is directly dependent upon the life 
of the cells causing fermentation. It occurs only when free oxygen is lacking to the 
cells, so that the latter must take oxj-gen from the chemical compounds in the nutrient 
fluid. In this way the molecular balance of the latter is destroyed. Acording to i:on 
JS'encki, anaerobiosis is to be regarded as the cause of the different kinds of fermentation. 

According to Nageli's moleciilar-physkal theory (Abhandl. der Bayr. Akad. JVlath.- 
physik., Kl. iii., Ser. 76, 1879), fermentation is a transfer of conditions of motion (which 
are present in all substances) from the molecules, atom-groups, and atoms of the differ- 
ent, chemically unchanged combinations constituting the living protoplasm to the 
material undergoing fermentation, whereby the molecular balance of the latter is dis- 
turbed and the molecules become disintegrated. 

According to E. and //. Buchner, there can be obtained from yeast, by a pressure 
of 400-500 atmospheres, a cell-juice which causes at once fermentation of sugar-solu- 
tions. Fermentation is, theref(n-e, not bound up with the life of the cells, but is caused 
by a cell-substance " zymase," which is probably secreted by the cell. This experi- 
ment has, indeed, been confirmed from other quarters, but the possibility that living 
protoplasm still remains in the expressed juice has not yet been excluded. 

The power to produce fermentation — i.e., decomposition — in a nutrient fluid is very 
likely a property, not only of the schizomycetes and blastomycetes, but also of the 
cells of more highly organized beings, even also of man. According to Voit Physi- 
ologic des Sauerstoff weclisels, " Leipzig, 1881), the decomposition of the dissolved albu- 
min circulating in the organism is to be referred to a fermentative activity of the cells. 
Pasteur has shown that fruit and leaves also possess fermentative properties under suit- 
5 able conditions. 

Besides the fermentation and decomposition caused by fungi, there are other de- 
compositions of organic substances in the production of which the fungi have no part. 
These consist chiefly in a slow oxidation or burning, in which carbonic acid and water 
are formed, and, in the case of nitrogenous substances, also ammonia. This form of 
decomposition takes place under conditions in which atmospheric air and moisture are 
in contact with organic matter. Moreover, it also takes place in the living organism. 
In the case of dead organic-matter, this biu-ning corresponds in part to the process 
commonly called mouldering. 

Literature. 

{Chemical Changes Produced by Schizomycetes.) 

Baumann u. v. TJdranszky : Vorkonmien von Diaminen (Ptomainen) bei Cystinurie, 

Zeitschr. f. phys. Chem., xiii., 1889. 
Bocklisch. Fiiulnissbasen aus Fischen. Ber. d. Deut. chem. Ges., xviii., 1885. 
Brieg-er: Ueber Ptomaine, Berlin, 1885, 1886; Berl. klin. AVoch., 1886; Zusammenset- 

zung des Mytilotoxins, nebst einer Uebersicht der bisher in ihren Haupteigenschaf- 

ten bekannten Ptomaine und Toxine. Virch. Arch., 115 Bd., 1889; Bakteriengifte. 

Zeitschr, f. Hyg., xix., 1895. 
Buchner: Active losliche Zellproductce. Munch, med. Wocli., 1897. 
Cahen: Ueb. d. Reductionsvermogen d. Bakterien. Zeitschr. f. Hyg., ii., 1887. 
van Ermengem: Anaerob. Bacillus u. seine Bez. z. Botulismus. Zeitschr. f. Hyg., 26 

Bd., 1897. 

Fermi : Die Leim und Fibrin losenden u. die diastatisclien Fermente der Mikroorgan- 

ismen. Cbl. f. Bakt., vii., 1890. 
Forster: Ueb. einige Eigenschaften leuclitender Bakterien. Cbl. f. Bakt., ii., 1887. 



INFECTION BY BACTERIA. 



551 



Gamaleia: Les poisons ?jacterieus, Paris, 1893. 

Gautier : Snr les alcaloi'des derives de la destruction bacterienue ou pliysiologique des 

tissiis aniniaux, ptomaines, et leucomai'nes, Paris, 1886. 
Hueppe: Ueb. die Zersetzungen der Milch vmd die biologisclien Grundlagen der 

Gahriingsphysiologie. Deut. med. Woch., 1884, p. 777; Mittheil. a. d. Kais. 

Gesundheitsamte, ii., Berlin, 1884. 
Ingenkamp: Unsere Kenntnisse v. Faulniss ii. Galirung. Zeitsclir. f. klin. Med., x., 

1885. 

Krannhals: Ueb. Kepliir u. lib. den Kepbirpilz. Deut. Arch. f. klin. Med., xxxv., 
1884. 

Lassar: Die Mikrokokken der Phosphorescenz. Pflliger's Arch., xxi., 1880. 
Ludwig: Die bish. Unters. iiber pathogene Bakterien. Cbl. f. Bakt., ii., 1887. 
Liideritz: Zur Kenntn. d. anagroben Bakt. Zeitschr. f. Hyg., v., 1888. 
V. Nencki: Zersetzung d. Gelatine u. d. Eiweisses bei d. Faulniss mit Pankreas, Bern, 

1874; verschied. Arb. im Journ. f. prakt. Cliem., im Journ. f. phys. Chem. u. in d. 

Ber. d. Deutsch. chem. Ges. a. d. J.., 1876-91; Die AnaGrobien u. d. Gahrungen. 

Arch. f. exp. Path., xxi., 1886. 
Pfllig-er: Pfliiger's Arch., 1875; Phophorescenz der lebendigen Organismen. Arch, f, 

d. ges. Phys., x., 1875; Phosphorescenz verwesender Organismen. lb., xi., 1875. 
Podwyssozki: Kephir, Petersburg, 1894. 

Salkowski: Zahlr. Arb. i. d. Ber. d. Deut. chem. Ges.; Zeitschr. f. phys. Chem, aus 

den letzten Jahren. 
Vaughan and Novy: Cellular Toxins, 1902. 

Winogradsky : Rech. sur les organismes de la nitrification. Ann. de I'lnst. Pasteur, 
1890, 1891. 

Wortmann: Ueb. d. diastatische Ferment d. Bakt. Zeitschr. f. phys. Chem., vi. ; 
Ptlanzl. Verdauungsprocesse. Biol. Cbl., iii. ; Organismen d. Nitrification u. ihre 
physiol. Bedeutung, Landwirthsch. Jahrb., xx., 1891; ref. Bakt. Cbl., x., 1891. 
See also §§ 148 and 150. 

2. General Considerations Concerning the Pathogenic Schizo- 
mycp:tes and their Behavior in the Human Organism. 

g 150. As has already beeu explained in §§ 11 and 12 there are among 
the schizomycetes nnmei'ous species which are capable of cansing disease - 
processes in the human organism, and are therefore called pathogenic 
schizomycetes. The first condition of su.ch action is evidently that the 
bacteria concerned must possess properties enabling them to multiply in 
the tissues of the living human body. They must therefore find in the 
tissues the suitable nutrient material, and in the body-temperature the 
warmth necessary to their g^rowth. The tissues, moreover, must not 
contain substances which are a hindrance to their growth (cf. §§ 30 
and 32). . ' 

If pathogenic fission-fungi succeed in growing in the tissues of the 
body, if infection takes place (cf. § 12), their action is in general char- 
acterized by the production, at the point of multiplication, of tissue-degener- 
ations, necrosis, inflammation, and new-growths of tissue, while at the same 
time the toxins produced by them cause manifestations of poisoning. 

In individual cases the pathological processes vary greatly, in that 
the distribution of the bacteria in the organism, and their local action, 
as well as the production of the poisons, differ greatly with the different 
forms of bacteria. 

With many the local action upon the tissue is the most prominent 
characteristic, with others the general intoxication. Many bacteria confine 
themselves to the region in which they have gained entrance ; others advance 
uninterruptedly upon the surrounding tissues ; others still are cai'ried by the 
blood and lymph streams and lead to the formation of metastatic foci, and, 
finally, others increase within the Mood. 

If a spread of the bacteria takes place through the blood, the bacte- 



552 



THE PARASITIC FISSION-FUNGI. 



ria may pass from the mother to the foetus during pregnancy, since the pla- 
centa forms . no certain filter against pathogenic bacteria. This has 
been demonstrated, for example, in the case of anthrax- bacilli, bacilli 
of symptomatic anthrax, glanders- bacilli, spirilla of relapsing fever, 
typhoid-bacilli, and the pnenmococcus. According to observations of 
Malvoz, Birch -Hirschf eld, and Latis, changes in the placenta, such as 
haemorrhages, loss of epithelium, and alterations of the vessel-walls, 
ftivor the passage of bacteria. Moreover, bacteria— as, for example, 
anthrax-bacilli — can grow through the tissue -spaces. In general the pas- 
sage of bacteria from the mother to the foetus presui^poses that after the 
entrance of these organisms into the circulating blood of the mother, the 
latter shall remain alive, at least long enough to allow of the passage of 
the bacteria into the foetus. 

The bacteria which succeed in multiplying within the human organ- 
ism die out again in many cases ivithin a short time ; and the disease pro- 
duced by them may proceed to recovery (cf. § 31). ^^^evertheless, it not 
infrequently happens that they are reserved for a longtime icithin the body, 
and either excite a continuous disease process, or at times remain in a con- 
dition of inactivity, so that no pathological processes are recognizable 
until after a longer or shorter period of latency, an active reproduction again 
takes place and manifestations of disease show' themselves anew. 

'Not infrequently a secondary infection associates itself with an infec- 
tion already existing. The relation between the two infections is either 
that the second infection follows the first accidentally, or that through the 
first infection the soil is prepared for the second (cf. § 12). 

Finally, there not infrequently occur double infections, in that two 
or more forms of bacteria develop coincidently in the tissues, and pro- 
duce their characteristic injurious influence wpon the tissues. 

Each pathogenic fission-fungus has a specific action upon the tissues 
of the human organism ; but, nevertheless, different species may exert a simi- 
lar action. For example, tliere are various bacteria capable of i3roducing 
suppuration. Only in a certain proportion of cases do the pathological 
tissue -changes show such siDCcific characteristics that from these the spe- 
cies of the pathogenic fission -fungus can be recognized with certainty. 

Further, it . has been demonstrated that pathogenic properties of 
bacteria are by no means constant ; that, on the contrary, their viru- 
lence varies, so that bacteria, which cause severe— that is, fatal — infec- 
tions may become changed (weakened) through external influences, so 
that they either wholly lose their power of causing disease-processes in 
the organism, or at least cause only mild forms of disease. This pecu- 
liarity is not alone of theoretical interest, but is also of great practical 
importance. It explains to a certain extent, on the one hand, why a 
certain infection does not always run the same course, and, moreover, 
why along with severe attacks light ones also occur. On the other hand, 
it affords us the i)0ssibility of obtaining material for inoculation from 
attenuated cultures of bacteria, by means of which mild grades of infec- 
tion or intoxication can be produced, which are able to protect the organ- 
ism from severe infections or to bring about the cure of an infection 
already acquired (cf. § 32). 

Weakening of tlie pathogenic properties of a f ission=f ungus can be 
brought about through the suitable action upon cultures of the same, by 
high temperatures, oxygen, light, or chemical antiseptic substances, as 
well as by the cultivation of the fungus in the body of a less susceptible 
animal. In some forms it is only necessary to cultivate the bacteria in 



ATTENUATION. METHODS OF BACTERIOLOGICAL INVESTIGATION. 553 



question for sometime upon artificial media (cliplococcus of pneumonia), 
or to expose the culture to the air for some time (bacillus of chicken- 
cholera), in order to bring about an attenuation. If it is desired to pre- 
serve the virulence of the pneumococcus for some time, it is necessary, 
from time to time, to pass the bacteria cultivated upon artificial media 
through rabbits, which are very susceptible. The glanders-bacilli, tu- 
bercle-bacilli, and the cholera-spirilla lose virulence when cultivated 
uninterruptedly upon artificial media for some time. The streptococcus 
of erysipelas (Emmerich) becomes so attenuated through continued cul- 
tivation in bouillon or nutrient jelly that it is no longer capable of kill- 
ing even mice. 

As to the nature of the attenuation of virulence of bacteria by the 
methods mentioned above, it is possible to give only hypotheses. If the 
bacteria cultivated for a long time upon artificial media change in viru- 
lence, this may perhaps be explained in part by assuming that in a series 
of generations the less virulent varieties, w^hich surely often arise, grad- 
ually gain the upper hand. For the attenuation of virulence by heat, 
chemical agents, etc., such an explanation is not adequate. In this case 
there is very probably a general weakening or degeneration of the proto- 
plasm, and in harmony with this theory is the fact that such bacteria 
show a diminution in energy of growth. 

If the presence of bacteria be suspected in any tissue-liuid or in the tissue-paren- 
chyma, tlieir demonstration may tirst be attempted by means of a microscopical 
investigation. Occasionally this is successful by the mere examination of a drop of 
the suspected fluid or of a smear-preparation of the tissue- juice diluted with salt-solu- 
tion or distilled water. In other cases it is necessary to employ staining methods, in 
which case cover-glass smears of the fluid are made and allowed to dry. The smeared 
cover-glass is then fixed by passing through the flame, and after cooling is stained. 
For this purpose methylene-blue is preferably emploj-ed, in a preparation of a one- 
per-cent. methylene-blue solution in a l-to-10,000 solution of caustic potash. Water 
solutions of fuchsin and methyl-violet are also frequently used. For many bacteria 
there are employed especial staining methods, in which ordinarily the preparations are 
heavily overstained with a solution of gentian-violet or fuchsin in aniline water, or with 
a water solution of methyl-violet, the excess of stain then being removed b}^ means of 
weak acids or by iodine and alcohol (Gram's metliod). In this way it is often brought 
about that the bacteria alone remain stained, often certain forms of bacteria only. 

When it is desired to demonstrate the presence of bacteria in tissues, small portions 
of the tissue are hardened in absolute alcohol, and are then cut into the thin vest possible 
sections loMch are stained by apjyropriate metliods. Here again the methods most fre- 
quently employed are those mentioned above : gentian-violet, methyl-violet, and fuchsin. 
Good objectives are necessary for the microscopic examination ; if possible, oil-immersion 
lenses and illumination with substage condenser should be employed. 

If through any metliod the presence of bacteria in the tissue has been demon- 
strated, the attempt is next made to cultivate them. For this purpose the methods 
developed by Kocli are usually employed. These, in principle, consist in obtaining 
first a fluid containing the bacteria; by means of scraping the tissue or by rubbing up 
pieces of tissue in sterilized salt-solution. This fluid is then evenly distributed in a 
solution of gelatin or agar which has been liquefied by warming ; and the mixture is 
then poured upon horizontal glass plates, solidifying as it cools. The individual bac- 
teria, or spores, thus separated from each other develop in the firm nutrient medium. 

By a proper application of this method there are obtained in the layer of gelatin 
various colonies (Fig. 414), which differ in appearance so that they may often be differ- 
entiated from each other by the naked eye alone. When sufficiently separated from 
one another, the individual colonies may be taken up by means of a fine platinum 
needle, and transferred either to* a boiled potato, or to a sterile gelatin plate, or streaked 
upon the surface of the solidified nutrient fluid in a test-tube. Very often the infected 
needle is stuck into the solidified transparent medium contained in a test-tube. 

If the culture on the gelatin plate is pure, and if the entire procedure is carried out 
with the necessary care and the avoidance of contamination, pure cultures may be ob- 
tained by this method. In stab-cultures, as well as in smear-cultures on potatoes or any 
other nutrient medium, special peculiarities often show themselves which make it pos- 
31 



554 



THE PATHOGENIC FISSION-FUNGI. 



sible for tiie experienced observer to recognize the form of bacteria. At times, how- 
ever, it is necessary to make a thorough microscopic examination of the colonies. 

It is evident that all the above manipulations must be carried out with care, and 
that absolute cleanliness of the instruments used — glass-plates and test-tubes — as well 
as perfect sterilization of the nutrient medium are necessary. The proper methods of 
sterilization in which a long-continued heating or an exposure to high temperatures 
plays an important role, are best learned in properly equipped laboratories. The neces- 
sary guidance is furnished in the various books on bacteriological methods of examina- 
tion, which have recently appeared. 

An infusion of meat containing peptone and gelatin is commonly employed for 
making plates. It consists of a watery infusion of chopped meat, to which a definite 
amount of peptone and salt is added. This is further neutralized with carbonate of 
soda, and enough gelatin is added to give a solid consistence at ordinary temperatures. 
For streak- and stab-cultures this same gelatin is sometimes used; at other times a 
jelly made of a mixture of a watery extract of meat, peptone, and agar-agar; or again 
blood-serum which has been coagulated by warming. 

For stab-cultures the jelly is allowed to solidify within the test-tube in a perpen- 
dicular position ; for streak-cultures the test-tube is kept in an oblique position until 
the jelly is set. 

Sterilized bouillon is often used for cultures. The inoculated nutrient media are 
kept either at room-temperature or at higher temperatures in an incubating oven 




Fig. 414.— Gelatin plate containing pellicle-like, sinuate cDlonics of siiuill bacilli, and small, spherical, white 
colonies of cocci. Culture made from the exudate of a purulent peritonitis. Reduced one-third. 



(30°-40° C). The proper nutrient medium to be used in individual cases m^ust be deter- 
mined by experiment. Experience has shown that the individual bacteria behave very 
differently in this respect, some growing best upon one, others upon another medium. 
To the nutrient medium there are often added with advantage such substances as sugar, 
glycerin, urine, brain-substance, etc. 

It is self-evident that the processes briefly described above may be modified accord- 
ing to the necessities of the case. For example, in those cases in which it is necessary 
to grow the bacteria at high temperatures, the use of gelatin should be avoided and 
agar-agar plates should be made instead. Occasionally membranes or exudates from 
mucous surfaces (diphtheria) or small bits of excised tissue are placed directly into the 
culture-medium. When it is desired to examine the cultures directly under the micro- 
scope, cultures may be made upon glass-slides. In the case of many bacteria, as 
cholera-spirilla, the use of hanging-drop cultures is advised. In this method a drop of 
sterilized bouillon hangs down from the under surface of a cover-glass, and is inocu- 
lated from a previously cultivated pure culture of the fungus. The cover-glass is then 
placed over the excavation in a hollow ground-glass slide. Evaporation is prevented 
by the exclusion of the outer air from the cavity in the slide, by a rim of oil or vaseline 
placed beneath the edge of the cover-glass. By this method the multiplication of bac- 
teria can be observed for a long time. 

When bacteria are sought in loater, a definite amount of the suspected water is dis- 



TISSUE CHANGES CAUSED BY BACTERIA. 



555 



tributed in gelatin, and plate-cultures are made. Earth is rubbed up witli sterilized 
salt-solution; rtzr is made to pass in definite amount through a sterilized salt-solution ; 
and the salt-solutions thus infected are then mixed with gelatin, and from this gelatin 
plates are made. 

The culture of bacteria on and in different media, accompanied by the microscopic 
examination of the different stages of development, serves for a more exact characteriza- 
tion, and thereby for the differentiation of the species of the bacteria in question. After its 
properties have been thoroughly studied in this way, the influence of the bacterium 
upon the animal organism is tested. As experimental animals, rabbits, dogs, guinea- 
pigs, rats, mice, and small birds are most frequently employed. The bacteria to be 
tested are introduced, sometimes under the skin, sometimes directly into the blood- 
current, sometimes by inoculation into the internal organs, sometimes by inhalation 
into the lungs, or sometimes by administration with the food into the intestinal canal. 
Bacteria can be regarded as pathogenic for a given animal when they multiply within 
the tissues and excite disease processes. If relatively large amounts are inoculated, the 
animal experimented upon may die under certain conditions, even if the bacteria do 
not increase at all in its body, since the poisonous substances formed in the culture and 
introduced by inoculation often suffice to kill the animal. 

Experience has taught that only some of the bacterial infections which occur in 
man, when inoculated into animals, run the same course as in man, and, indeed, only 
those which also occur otherwise in animals. In other cases the pathogenic fission- 
fungi occurring in man or in certain animals are, it is true, pathogenic for the experi- 
mental animal, but the pathological process shows another localization and another 
course. In a third case the experimental animals are in part or wholly immune. 

Inversely, fission-fungi that are often extremely pathogenic for the experimental 
animals are harmless for other animals or for man. 



Literature. 

(Local Tissue -changes in Bacterial Infections.) 

Bard: Characteres anat.-pathol. generaux des lesions microbiennes. Arch, de phys., 
ix., 1887. 

Baumgarten : Zur Kritik der Metschnikoff'schen Phagocytentheorie. Zeitschr. f. klin. 
Med., XV., 1888; Das Experimentum crucis d. Phagocytenlehre. Beitr, v. Ziegler, 
vii., 1890. 

Birch.-Hirsch.feld: D. Eindringen v. Darmbakt. in d. Innere d. Organe. Beitr. v. 

Ziegler, xxiv., 1898 (Lit.). 
Buchner: Die chem. Reizbarkeit d. Leukocvten und deren Beziehung z. Entzundung 

u. Eiterung. Berl. klin. Woch., 1890; Cbl. f. Bakt., ix., 1891. 
Cattani: Ueb. d. Reaction d. Gewebe auf specif. Reize. Beitr. v. Ziegler, vii., 1890. 
Faulhaber: Bakterien in d. Nieren b. acuten Infectionskraukheiten. Beitr. v, Ziegler, 

X., 1891. 

Flexner : The ^Pathologic Changes Caused by Certain Toxalbumins. The Med. News, 
1894. 

Gamaleia: Sur la lesion locale dans les maladies microbiennes. Arch, de med. exp., 
ill., 1891. 

Goldscheider u. Mliller: Phagocytose. Fortschr. d. Med., xiii., 1895. 
Hess: Unters z. Phagocytenlehre. Virch. Arch., 109, 110 Bd., 1889. 
Janowski: Die Ursachen d. Eiterung. Beitr. v. Ziegler, xv., 1894. 
Leber: Entsteh. d. Entzundung. Fortschr. d. Med., vi., 1888. 

Lewin: Histol. d. acut. bakt. Entzimdungen. Arb. a. d. path. Instc zu Tiibingen, i., 
1891. 

Massarl et Rodet: Le cliimiotaxisme des leucocytes et i'infect. microb. Ann. de 
I'Inst. Pasteur, 1891. 

Metschnikoff: Sprosspilzkrankheit d. Daphnien. Virch. Arch., 96 Bd.. 1884; Be- 
ziehung d. Milzbrandbacillen z. d. Phagocyten. lb., 97 Bd., 1884; Pathol. Bedeu- 
tung d. intracellularen Verdauung. Fortschr. d. Med., iii., 1884; Kampf d. 
Zellen geg. Erysipelkokken. Virch" Arch., 107 Bd., 1887; Phagocytenkampf beim 
Riickfalltyphus. lb., 109 Bd., 1887; Sur la lutte des cellules de Torganisme centre 
I'invasion des microbes. Ann. de I'Inst. Pasteur, i., 1887; Offener Brief an Weigert. 
Fortschr. d. Med., vi., p. 81; Phagocytare Rolle der Tuberkelriesenzellen. Virch. 
Arch., 113 Bd., 1888; Verhalten der !5lilzbrandbakterien im Organismus. lb., 114 
Bd., 1888; Destruction des bacteries. Ann. de I'Inst. Pasteur, 1895. 

Netschajeff: Bedeutung der Leukocyten bei der Infection. Virch. Arch., 125 Bd., 
1891. 



556 



THE PATHOGENIC FISSION-FUNGI. 



Pernice et Alessi : Le altera-zioni del sangue nelle infezioni sperimentali. La Sicilia 
Med., ii., 1891. 

Prudden and Hodenpyl : Action of Dead Bacteria in the Living Body. New York 
Med. Joiirn., 1891. 

Ribbert: Scliicksal patliogener Pilze im Organismus. Deut. med. Woch., 1885; Der 
Untergang pathogener Scliimmelpilze im Korper. Bonn, 1887; Ueber wiederiiolte 
Infectionen mit pathogenen Schimmelpilzen. Deut. med. Woch., 1888; Verlauf 
der durch Staphylococcus aureus in der Haut von Kaninclien hervorgerufenen 
Entzlindungen. lb., 1889; Die patholog. Anatomic und die Heilung der durch 
den Staphylococcus p3'ogenes aureus hervorgerufenen Erkrankungen, Bonn, 1891. 

Rog-owitsch. : Wirkung d. Rauschbrandbacillus auf d. thier. Organismus. Beitr. v. 
Ziegler, iv., 1889. 

Rufier: Destruction des microbes par les cellules amiboi'des. Ann. d. I'lnst. Pasteur, 
v., 1891. 

Stschastny : Beziehungen der Tuberkelbacillen zu den Zellen. Virch. Arch., 115 
Bd., 1889. 

Tschistovitsch : Etude surla pneumonic fibrineuse. Ann. de I'lnst. Pasteur, v., 1891. 
Virchow: Der Kampf der Zellen und der Bakterien. Virch. Arch., 101 Bd., 1885. 
Weigert: Ueber Metschnikoff 's Theorie der tuberculosen Riesenzellen. Fortschr. d. 
:Med., vi. 

Wyssokowitscli : Schicksal ins Blut injicirter Mikroorganismen. Zeitschr. f. Hj'g., 
i., 1886. 

Ziegler : Die Ursachen u. das Wesen der Immunitat des menschl. Organismus gegen 
Infectionskrankheiten. Beitr. v. Ziegler, v., 1889; Ursachen d. Gewebsneubildun- 
gen. Intern. Beitr. z. wiss. Med., Festschr. f. Virchow, ii., Berlin, 1891; Entziin- 
dung. Eulenb. Realencyklop ; Ueber die Zweckmassigkeit d. pathol. Lebensvor- 
gange. Miinch. med. Woch., 1896. 

(Ftoma'ins and Toxins, and their Relations to the Infectious Diseases.') 
Arloing: Les virus, Paris, 1893. 

Backlisch.: Ptomaine aus Fischen. Ber. d. chem. Ges.. xviii., 1885. 
Beck: Unters. in d. Geb. d. Anatomic, Phys. u. Chir., Karlsruhe, 1852. 
V. Bergmann: Das putride Gift u. d. putride Intoxication, Dorpat, 1868; Cbl. f. d. 
med. Wiss., 1868. 

Billroth: Unters. lib. die Vegetationsformen d. Coccobacteria septica, Berlin, 1874. 
Blumberg: Putride Intoxication. Virch. Arch., 100 Bd;, 1885. 

Bouchard: Action des produits secretes paries microbes pathog., Paris, 1890; Theorie 

de I'infection. Verb. d. X. intern, med. Congr., i., Berlin, 1891; Les microbes 

pathogenes, Paris, 1892. 
Brieger: Aetiol. d. Wundstarrkrampfs. Biol. Centralbl., vii., 1887; Tetanin u. My- 

tilotoxin. Virch. Arch., 112 Bd. ; Zusammensetzung d. Mytilotoxins nebst 

Uebersicht d. bisher in ihren Haupteigenschaften gekannten Ptomaine und Toxine. 

Virch. Arch., 115 Bd.; Ueber Ptomaine, i.-iii., Berlin, 1885-86; Bakterien u. 

Krankheitsgifte. Biol. Centralbl., x., 1890; Beziehungen d. Fauluissproducte zu 

Krankheiten. Zeitschr. f. khn. Med., iii. Bd. 
Brieger u. Fraenkel, C: Unters. lib. Bakteriengifte. Berl. klin. Woch., 1890. 
Brieger u. Wassermann : Auftreten v. Toxalbuminen b. Menschen. Char. -Ann., 

xvii., 1892. 

Cbarrin: La maladie p^'ocyanique, Paris, 1889. 

Cbarrin et Gley : L'action des produits secretes par le bacille pyocyanique sur le sys- 

teme nerveux. Arch, de phys., iv., 1890, v., 1891. 
Debierre: Les maladies infectieuses, microbes, ptomaines, leucomaines, Paris, 1888. 
Duclaux: Ferments et maladies, Paris, 1892; Le microbe et les maladies, Paris, 1886; 

Sur les phenomenes generaux de la vie des microbes. Ann. de I'lnst. Pasteur, i., 

1887; Les matieres albuminoides. lb., v., 1892. 
van Ermengem: Anaerobe Bac. u. s. Bezieh. z. Botulismus. Zeitschr. f. Hyg., 26 

Bd., 1897. 

Gaffky u. Paak: Wurst- und Fleischvergiftung. Arb. a. d. K. Gesundheitsamte, vi. ; 

ref. Cbl. f. Bakt., viii., 1890. 
Gamaleia: Les poisons bacteriens, Paris, 1892. 
Hiller: Die Lehre vo'n der Fiiulniss, Berlin, 1879. 

Hoffa: Zur Lehre der Sepsis u. des Milzbrandes. Langenbeck's Arch., 39 Bd., 1889. 
Huseniann: Ueber Ptomaine. Arch. d. Pharmacie, 1880-83. 
Jacquemart: Les ptomaines, Bruxelles, 1890. 

Koch: Untersuchuugen liber Wundinfectionskrankheiten. Leipzig, 1878. 
Leber: Die Entstehung der Entziindung, Leipzig, 1891. 



DOUBLE AND SECONDARY INFECTION. 



667 



Otto: Anleit. z. Ausmittelung d. Gifte, Braunschweig, 1883. 

Paltauf u. Heider: Der Bacillus maidis u. seine Beziehungen z. Pellagra. Med. 
Jahrb., 1889. 

Panum: Das putride Gift, die Bakterien, putride Intoxication u. Septikamie. Virch. 
Arch., 60 Bd., 1874. 

Poucliet: Matieres extractives, ptomaines et leucomaines. Revue de med., vii., 1887. 
Sahli: Moderne Gesichtspunkte in d. Path. d. Jnfectionskrankh. Kl. Vortr., Nos. 
319-320, 1888. 

Sclnniedeberg u. Harnack: Bildung von Muscarinaus Neurin. Arch. f. exp. Path., 
xvi., 1883. 

Selmi: Berichte d. Deutsch. chem. Ges., vi., vii., and xii. ; Ptomaine o. Alcaloidi 
cadaverici, 1881. 

Trambusti: Physiol. Wirkung v. Hydrophilus fuscus. Beitr. v. Ziegler, xiv., 1893. 
Vaughau and Novy : The Cellular Toxins, Philadelphia, 1902. 
See also §§ 12 and 149. 

(Transmission of Bacteria from the Mother to the Foetus.) 

Alilfeld: Milzbrand des Neugeb. nach Infection d. Mutter. Ber. u. Arb., iii., Leipzig, 
1886. 

Birch-Hirschfeld : Pforten der placentaren Infection des Fotus. Beitr. v. Ziegler, 
ix., 1891. 

Bolling-er: Uebergang path. Organismen v. d. Mutter auf d. Kind. Miinch. med. 
Woch., 1887. 

Eberth: Geht der Typhusorganismus auf den Fotus liber? Fortschr. d. Med., vii., 
1889. 

Ernst: Intrauterine Typhusinfection einer lebensfahigen Frucht. Beitr. v. Ziegler, 
viii., 1890. 

Hildebrant: Zur Casuistik d. placentaren Uebergangs d. Typhusbacillen. Fortschr., 
vii., 1889. 

Kockel u. Lungwitz: Placentartuberculose beim Rind, Beitr, v. Ziegler, xvi., 1894. 
Latis: Uebergang d. Milzbrandes v, d. Mutter auf d. Fotus. Beitr, v, Ziegler, viii., 
1890. 

Loflier : Die Aetiologie der Rotzkrankheit. Arb. a. d. Kais. Gesundheitsamte, i. , 1886. 
Lubarscli: Intrauterine Uebertragung pathogener Bakterien. Virch. Arch., 124 Bd., 
1891. 

Malvoz: Sur la transmission intraplacentaire des micro-organismes. Ann. de ITnst. 

Pasteur, ii. , 1888 ; Le passage des micro-organismes au foetus. lb. , iii. , 1889. 
Marchand: Milzbrand b. einer Schvvangeren m. Infection d. Kindes. Virch. Arch., 

104 Bd., 1887. 

Netter: Transmission intra-uterine de la pneumonic. Arch, de biol., 1889. 
Perroncito e Carita: De la transmission de la rage. Ann. de I'lnst. Pasteur, 1., 1887. 
Sclimorl u, Kockel: Tuberculose der mensclil. Placenta. Beitr. v. Ziegler, xvi., 1894. 
Straus et Chamberland : Rech. exper. sur la transmission de quelques maladies viru- 

lentes, en particulier du cliarbon, de la mere au foetus. Arch, de phys., i., 1883. 
Rosenblath. ; Uebergangsfahigkeit d. Milzbrandbacillen v. d. Mutter auf d. Kind. 

Virch. Arch., 115 Bd., 1889. 
Wolff: Vererbung von Infectionskrankheiten. Virch. Arch., 112 Bd., 1888. 

{Double hifection and Secondary Infection. ) 

Babes : Recherches sur les associations bacteriennes du bacille de la tuberculose. Le 
Progres med., Roumain, 1888; ref. Cbl. f. Bakt., v., 1888; Bakteriol. Unters. liber 
septische Processe d. Kindesalters, Leipzig, 1889; Les associations bacteriennes. 
Verb. d. X. internat. med. Congr., ii., Berlin, 1891; Ueber einige bei Influenza 
gefundene Bakterien. Cbl. f. Bakt., vii., 1890; Associat. bacter. du bac. de la 
tuberculose avec des microbes hemorrliagiques. La Roumaine med., xv., 1893. 

Barbier: De quelques associat. microbiennes dans la diphtheric. Arch, de med. exp., 
iii., 1891. 

Bein: Bakteriolog. Unters. iiber Influenza. Zeitschr. f. klin. Med., xvii., 1890. 
Buchner: Bakteriolog. Befunde bei d. letzten Influenzaepidemie. Miinch. med. 
Woch., 1889. 

V. Dung-ern: Mischinfection bei Diphtheric. Beitr. v. Ziegler, xxi., 1897. 
Hericourt: Les associations microbiennes. Revue de med., vii., 1887. 
Heubner: Ueber die Scharlachdiphtherie. Samml. klin. Vortr., No. 322, 1888. 
Lenhartz: Secundarinfectionen bei Scharlach. Jahrb. f. Kinderheilk., xxvii., 1888. 



558 



THE PATHOGENIC FISSION-FUNGI. 



Polg-uere: Les infections secondaires, leurs localisations secondaires au cours de la 

tievre typhoi'de et de la pneumouie, Paris, 1888. 
Raskin: Unters. liber Secondariufectioueu bei Scliarlach. Cbl. f. Bakt., v., 1889. 
Ribbert: Bakt. Mittlieil. liber Influenza. Dent. med. Wocli., 1890. 
Romberg: Beobacht. lib. Leberabscesse b. Typhus abdominalis. Berl. klin. Woch. 

1890. 

Rosenbacb.: Mikroorganismen bei den Wundinfectionskranklieiten, Wiesbaden, 1884. 
Sata: Ueber die Bedeutung der Miscliinfection bei der Lungenschwindsucht, Jena, 
1899. 

Weichselbaum: Bakteriolog. und anat. Unters. liber Influenza. Wien. klin. Woch. 
1890. 

{Changes in the Physiological Froperties [Attenuation'] of Bacteria,) 

Adami: On the Variability of Bacteria. Med. Chronicle, September, 1891. 

Arloing, Thomas, Cornevin: Du charbon symptomatique, Paris, 1887. 

Bucliner: Die Nageli'sche Theorie der Infectionskrankheiten, Leipzig, 1878; several 

articles in NaQeli's Unters. lib. nied. Pilze, 1882; Immunitat u. Immunisirung. 

Mlinch. med. Woch., 1889. 
Chauveau : Rech. sur le transf ormisme en microbiologic pathogene ; des limites, des 

conditions et des consequences de la variabilite du bacillus anthracis. Arch, de 

med. exp., 1889. 

Fliig-ge: Abschwachung virulenter Bakterien u. erworbene Immunitat. Zeitschr. f. 

Hyg., iv., 1888. 
Gaifky: Mittheil. a. d. K. Gesundheitsamte, i., 1881. 
Hueppe: Die Formen der Bakterien, Wiesbaden, 1886. 

Kocli: Wundinfectionskrankheiten, 1878. Mittheil. a. d. K. Gesundheitsamte, i., 1881; 

Ueber die Milzbrandimpfung, Berlin, 1882. 
Koch, Gaff ky-Lioffler : Abschwachung d. Milzbrandbacillen. Mitth. a. d. K. Ges.- 

Amt., ii., Berlin, 1884. 
Lubarsch: Abschwachung d. Milzbrandbacillen im Froschkorper. Fortschr. d. Med., 

vi.. 1888. 

Nageli: Die niederen Pilze, 1877; Untersuchungen liber niedere Pilze, Mlinchen, 1882. 

Pasteur: Sur les maladies virulentes et en particulier sur la maladie appelee vulgaire- 
ment cholera des poules. Acad, de med., 19 fevr., 1880; Sur le cholera des poules, 
etude des conditions de la nou-recidive de la maladie. Acad, de med., 27avr., 
1880; Attenuation du virus du cholera des poules. Acad, des sciences, 26 oct., 
1880; De I'attenuation du virus. Congres internat. d'hyg. a Geneve, 1882; zahl- 
reiche Mittheilungen in den Berichten der Acad, de med. aus den Jahren, 1880-89 
(cf. Rodet). 

Pasteur et Throllier : Abschwachung des Giftes des Rothlauf es der Schweine durch 
Impfung auf Kaninchen. Compt. rend., xcvii., 1883. 

Rodet: L'attenuation des virus. Revue de med., vii., 1887, viii., 1888; De la varia- 
bilite dans les microbes, Paris, 1895. 

Schottelius: Untersuch. lib. Micrococcus prodigiosus. Festsch. f. v. Kolliker, Leip- 
zig, 1887. 

Viala: Sur les causes de l'attenuation des moelles rabiques. Ann. de I'lnst. Pasteur, 
v., 1891. 

Wasserzug : Variations de la forme et de la fonction chez les bacteries. Ann. de 
I'Inst. Pasteur, 1888. 

{Methods of Bacteriological Investigation. ) 

Abel: Taschenbucli f. bakteriologische Praktikanteu, Wiirzburg, 1900. 
Crookshank : An Introduction to Practical Bacteriology, London, 1886. 
Fischer: Vorlesungen liber Bakterien, Jena, 1897. 
Fliigge: Die Mikroorganismen, Leipzig, 1896. 
Fraenkel, C. ; Grundriss der Bakterienkunde, Berlin, 1890. 
Glinther : Einf lihrung in das Studium der Bakteriologie, Leipzig, 1898. 
Hueppe: Die Me thoden der Bakterien forschung, Wiesbaden, 1891. 
V. Kahlden: Technik der pathol.-anat. Untersuchungen, Jena, 1900. 
Migula: Bakteriologisches Praktikum, Karlsruhe, 1892. 
Novy : Laboratory Work in Bacteriology, 1899. 

Numerous articles on the investigation of bacteria are found in the Centralblatt f. 

Bakteriologie. 



THE COCCI. 



559 



II. The Different Forms of Bacteria and the Infectious Diseases 

Caused by Them. 

I. The Cocci, ok Sph^robacteria, and the Morbid Processes 

Caused by Them. 

(a) General Considerations Regarding the Cocci. 



§ 151. The cocci or coccacese (Zopf) are bacteria that occur exclu- 
sively in the form of round or oval or lanceolate cells. In their multi- 
plication by division they often form peculiar aggregations of cells, 
which are commonly designated by special names according to the char- 
acter of the different forms appearing. Since certain forms of cocci are 
especially likely to develop in definitely shaped aggregations, advantage 
has been taken of this fact, to classify them in different species. It 
should be noted, however, that a given species does not always appear in 
the same form, but may vary according to the nutrient conditions. 

Many of the cocci multiply by division in one plane only — at right 
angles to the length of the elongated spherical cell. If the spheres re- 
sulting from division remain together for some time in the form of double 
spheres, and if this 
form - appears with 
especial frequency in 
the case of any one 
species, it is desig- 
nated as a diplococcus 



Fig. 415. 




Fig. 417. 




Fig. 416. 



Fig. 418. 



Fig. 415.— streptococcus from a purulent peritoneal exudate of a case of puerperal peritonitis, a, 
Single cocci ; />, diplococci ; c, streptococci or torula-chains. x 500. 

Fig. 416.— Colonies of micrococci in blood-capillaries of the liver, causing metastatic abscess-formation. 
From a case of pysemia. Necrosis of liver-cells. X 400. 

Fig. 417.— Cocci grouped in tetrads (merismopedia), from a softening infarct of the lung. X 500. 

Fig. 418.— Sarcina ventriculi. X 400. 



(Fig. 415, If, from a further continued division of the cells in one 
plane, rows of cocci {torula chains) result, these are known as strepto= 
cocci (Fig. 415, e), and this term is used also as the name for a group. 
If the division of the cells takes place irregularly, and the cells remain 
together in small collections or heaps, the bacteria are usually desig- 
nated as micrococci (Zopf) (Fig. 416). By Ogston and Eosenbach 
the name staphylococcus or grape-coccus has been used to indicate some 
of these forms. Larger collections of cells, which are held together by 
a gelatinous substance derived from the cell-membranes, have been 
designated as zodgloea masses. If the masses of cocci are united into 
larger collections by means of a gelatinous envelope, they are spoken of 
as ascococci or tube-cocci. 

To those cocci which remain united for a long time in a four-celled 
tablet (Fig. 417), the name of merismopedia, tetracoccus or tablet=coccus 



560 



THE PATHOGENIC FISSION-FUNGI. 



was applied by Zopf. Others class such bacteria with the micrococci. 
The cocci that go by the name sarcinae are characterized by division in 
three directions of space, so that compound cubical j)ackets of spherical 
cells are formed from tetrads (Fig. 418). 

The cocci not infrequently show a tremulous molecular motion in 
fluids; swarming movements have not been observed with certainty. 
Spore-formation has not been demonstrated in the majority of forms. 
According to Cienkowski, Yan Tieghem, and Zopf, the Coccus (leuconos- 
toc) mesenterioides, that produces a frog-spawn-like culture on sugar or 
parsnips, forms arthrogenic spores, in that some particular cell in a 
torula chain becomes larger and glistening. According to Prazmowsky 
the Micrococcus urece also forms spores. 

The saprophytic cocci grow upon very different nutrient substrata 
and cause by their growth in suitable media various processes of de- 
composition. Many also form pigments. Micrococcus urece (Pasteur, 
Yan Tieghem, Leube) causes fermentations in urine by means of which 
ammonium carbonate is formed from the urea. Micrococcus viscosus is 
the cause of the slimy fermentation of wine. The cause of th.Q pliosplior- 
escence of decomposing meat was found by Pfliiger to be a micrococcus that 
forms slimy coatings on the surface of the meat. 

Of the pigment-producers the best known are Micrococcus luteus, Mi- 
crococcus am^antiacus, Sarcina lutea, Micrococcus cyaneus and Micrococcus 
violaceus, which, when grown upon boiled eggs or potatoes, produce yel- 
low, blue, and violet i)igment respectively. 

Saprophytic cocci are found in the mouth cavity and intestine, as 
well as on the sui^face of the skin, and occasionally also in the lungs. 
Micrococcus Jiwmatodes (Babes) is said to be the cause of red sweat, and 
forms red zoogloea masses. 

Sarcina ventriculi (Fig. 418) occurs not infrequently in the stomach 
of man and animals, especially when abnormal fermentations are going 
on. According to Falkenheim the stomach sarcines can be cultivated 
upon gelatin, and form in this medium round, yellow colonies, which 
contain colorless monococci, diplococci, and tetrads, but never cubical 
packets. They form these, however, in neutralized hay-infusion, and 
their growth causes a souring of the infusion. The membrane of the 
sarcinge is said to consist of cellulose. 

Microcococcus tetragenus (merismopedia) is not infrequently found 
in human sputum, and in the mouth and throat; it may be present 
further in the wall of tuberculous cavities, or in hsemorrhagic or gan- 
grenous foci of the lungs. It forms tetrads (Fig. 417) whose cells are 
held together by a gelatinous membrane. On gelatin -plates it forms 
round or oval, lemon-yellow colonies. It is pathogenic for white mice 
and guinea-pigs, to a less extent for rabbits, and, when injected subcuta- 
neously, excites purulent inflammations, in the mouse often also a sep- 
ticgemia. Intratracheal injections may give rise to inflammations of the 
respiratory passages and the lungs. 

The pathogenic cocci cause acute inflammations whicb usually heal 
after the death of the bacteria; but it not infrequently happens that 
cocci may remain in the body for a long time and give rise to chronic 
processes. 



TEE PATHOGENIC COCCI. 



501 



Literature. 

{The Cocci.) 
Babes: Rother Seliweiss. Biol. Cbl., ii., 1882. 

Bancel et Hasson ; »Sur la phosphorescence de la viande de homard. Compt. rend., 
t. «8, 1879. 

Bienstock: Baktcrien d. Darmes. Fortschr. d. 3Ied., i. ; Zeitsclir. f. klin. ]VIed., vii.. 
1884. 

Bosc et Galavielle: Sur le micrococ. tetrageuus. Arch, de med. exp., 1899. 
Brieg-er: J3akterien des Darmes. Berk klin. Woch., 1884. 

Chauffard et Raymond: Septicemic tetragenique. Arch, de med. exp., 1896. 
Cohn: Beitriige z. Biologic d. Ptlanzen, i.-iv. 
Eberth: Blauer Eiter. Yirch. Arch., 73 Bd., 1878. 

Eschericli: Baktcrien d. Darmes. Fortschr. d. Med., iii., 1885; Munch, med. AVoch., 
1886. 

Falkenheim : Ueber Sarcine. Arch. f. exp. Path., xix., 1885. 

Gessard: De la pyocj^auine et de son microbe. These de Paris, 1882. 

Liicke: Blauer Eiter. Arch. f. kiln. Chir., 1892. 

Ludwig: Micrococus Ptlugeri (Phosphorescenz), Hedwigia. 1884. 

Miller: Die Mikroorganismeu der Mundhohle, Leipzig, 1892. 

Prazmowsky: Ueber Sporenbildung bei den Baktcrien. Biol. Cbl., viii., 1888. 

Prove: ^Micrococcus ochroleucus. Beitr. z. Biol. d. Pflanzen v. Cohn, iv., 1887. 

Schroter: Pigmentbildende Baktcrien. Beitr. z. Biol. d. Ptlanzen, v., Cohn, i. 

Stubenrath. : Das Genus sarcina, ]Munclien, 1897. 

Vignal: liech. s. 1. nncroorganismes de la bouche. Arch, de phys., viii., 1886; Rech. 
s. 1. microorg. des matieres fecales. lb., x., 1887. 
See also § 148. 

(h) The Pathogenic Coed. 

g 152. The Streptococcus pyogenes (Rosenbach) is a coccus which, 
iu multiplyiug, forms doiihle spheres and chains of spheres (Fig. 415 ) of 
different lengths, containing from four to twelve or more cells. This 
chain-formation comes to an especially full development when the strep- 
tococcus is growing in Huids — in nutrient bouillon or fluid exudates — but 
is also usually seen when it is growing within the tissues. 

The cocci stain well by Gram's method, are facultatiA C anaerobes, 
grow best at 37° C, and form small whitish colonies on gelatin and agar. 

The strei^tococcus pyogenes is especially pathogenic for mice and 
rabbits (much less so for dogs and rats) ; but its virulence varies greatly, 
and rapidly decreases in cultures grovrn on ordinary media. Its virulence 
is retained for a relatively long time (Marmorek) in cultures of the cocci 
in human- or iu horse-serum (serum two parts, bouillon one part), or in 
a mixture of bouillon and ascitic fluid. 

Streptococcus pyogenes causes in man inflammations, tchich usually, 
though not always, assume a purulent character. Occasionally it is found 
also \ij)on normal mncous membranes, for example, in the upper air-pas- 
sages, or in the vagina and cervix uteri; it may therefore be assumed in 
such cases that its virulence is verj^ slight, or that the mucous membranes 
offer a successful resistance to its entrance into their tissaes. 

An infection with streptococci may occur either in healthy indi- 
viduals, or in those who have received some injury, or Anally as an ac- 
companiment and secjuela of other infections, particularly of scarlet 
fever, diphtheria, and pulmonary tuberculosis. 

If the streptococcus multiplies upon the snrface of mucous memhranes — 
foi' example, of the respiratory tract (Fig. 419 ) — it excites an inHamma- 
tion, whicli may bear the character of a desquamative or pumJent catarrh 



562 



THE PATHOGENIC FISSION -FUXGI. 



(c), or of a croupous e.rudafion ((/). If it penetrates into tlie connective 
tissues of the siibniucosa, it causes most frequently intiammations which 



b 
d 

a 



9S 


7,4 




Ho 


'if 


Is 








u 



^^r- 



Fig. 419.— streptococcus tracheitis in scarlet fever (alcohol, carmine, methyl-violet. iodineV a. Con- 
nective tissue: b, desquamated epithelium; c, membrane composed of cells and streptococci; (?. fihnn- 
threads. X 300. 



Fig. 420,— Streptococcus pyo.eenes from a phlegmon- 
ous focus of the stomach (alcohol, carmine, methyl- 
violet, iodine), a, Leucocytes ; /). leucocytes containing 
streptococci ; c, free streptococci. X 5(X). 



are pMegmonous in character — i.e., a more or less quickly spreading, sero- 
purulent, or purulent, or fibrinopurulent, or serofibrinous inflamma- 
tion, which may at certain points lead to supjDuratiou and abscess-for- 
mation. In the exudate the 
cocci may be found in part free 
"\ (Fig. 420, c), or in part inclosed 

\ ' .,s-^ f V, • V:: within cells (&). 

V. If the streptococcus spreads 

.-A-^r*- / ^'C. -'V', ill corium, into which it pen- 

Vi'>; ' „ ^ / '^.^ s et rates especially in the case of 

*' * "^Z small wounds of the skin, it util- 

V'"* *• izesthel^mph-spacesandlymph- 

/ vessels (Figs. 421, a ; 422, /?, /: 

423, c) as pathways and as 
places for the development of 
colonies, causing a more or less 
severe inflammation, which is 
characterized macroscopically by an ad\'ancing redness and swelling of the 
skin known as erysijyeJas. To the external appearances there corresponds 
a more or less severe serous and cellular infiltration (Figs. 421, d, e, f ; 
422, m; 423, e), and often 

also a fibrinocellular exuda- ? y» 

tion (Fig. 422, m,). The in- 
fection of the lymph -vessels 
in erysipelas involves at 
times chiefly the superficial 
layers of the cutis (Fig. 
422), at other times the 
deeper lavers (Fio\ 423, c). 

In fhp p-T^P thp Prvc;iii ^^'^■Streptococcus cni^^ipdaUs (a) inside a lyraph- 

iii Liie iciiit^i Lci^t? Liif fi \ vessel (h), in part composed of thickly crowded spheres, in 

elatOUS process becomes P^'"^ torula-chalns (alcohol. £rentian-violet>; c. neigh boi- 

^ • ^ 1 . hood of the Ivmph-vessel. with pale, non-stainins nuclei ; (7, 

phle2:monOUSin character, so vein: f, nenveaous cellular infiltrati.ui of tissue; f. accumu- 

tliof "VkAfwfiAn fliA two i-k-pn^^ ^^^^^^ of ''"-■^ ^'^^ lymph-vessel. Section of rabblfs ear 

mai ueL\\een me IWU piOC- two days ^tfter inoculation with erysipelas-cocci. X225. 




STREPTOCOCCUS PYOGENES. 



563 



esses a sharp border-liue caimot be drawn. At tlie same time with tlie 
infection of the deeper hiyers streptococci may spread on the snrface of 
the epithelium — that is, beneath the horny hiyer (Fig. 423, g), and cause 

d 




Fig. 433.— Section of the skin in erysipelas biillosum (alcohol, alum-carmine), a, Epidermis; b, 
coriuin ; c, vesicle ; (?, covering' of vesicle ; e, epithelial cells containins: vacuoles ; / swollen cells with 
swollen nuclei: f/, gj, cavity caused by the liquefaction of epithelial cells, and containing fragments of 
epithelium and pus-corpuscies ; //, lymph-vessel, partly filled with streptococci ; /. lyuii>h-vessel filled full of 
streptococci; 7f, colony of streptococci in the tissue; Z, /j, necrotic tissue; m, cellular, //Jx, fibrinocellular 
infiltration ; », fibrinocellular exudate in the vesicle. X liO. 




Fig. 433. -Erysipelas of the head in a child of one month of age (bacterial staining, carmitie). ct. Cutis 
with hair-follicles; f), siibcutis; c, lymph-vessel with streptococci and inflamed surrounding area; ci, rete 
Malpighii ; c, /, horny layer ; streptococci lying upon the rete Malpighii. X 45. 



561 



THE PATHOGENIC FISSIOX-FUXGT. 



a loosening of the epirhelial cells and a desqnamation of the horny layer 
(/). In cases of sevei-e infection with very virulent streptococci the 
process may go on to liquefaction of the epithelinni (Fig. 422, e, f, g, 
f/J, and to the formation of vesicles (<?, erysipelas bnllosnm), or to ne- 




yi>. _ ' - ■ ii -'ccus phlegmon on the trunk, after phlesnuin of the arm (formalin, ear- 

n.r. . ■ : c. >trL-piue'.'rei in the subeutant'ous conuertive tissue; J. beginning cul- 

crosis and gangrene of the coriuni (7, J^, erysipelas gaiigrfenosnm), or to 
snxDpnration of the tissue. 

In the subcutaneous fissiir the spread and multiplication of the cocci 
TFig, 424. c i lead to a progressive seropurulent t d ^ and fibrinopurulent 
intianiniatit '11. often Avitli suljset.iueut tissue-suppuration. Such forms of 
infection aro known as (^//.s-. 

If tlie /// //.s'-> .s Jifrimif l/trnJrf(l hi a jilthgriionous process, the streptococci 
increase and spread cliietly in the connecti\'e tissue of the perimysium 
interniun, but may penetrate also into the sarcoh^nnna-tubes. Here also 
the conseqitences of the infection are more or less severe inflammations 
leading to siippurailon. 

Bronclinf/f iini'.s iiiffrilnn of tJ/f ///////x causes purulent, or croupous, or 
ht'emorrhai:ir exudauons intt» tlie imhaonary ah'eoli. 

Should bone become involved from tlu^ >kin or from a mucous mem- 
brane — as, for example, from the middle ear— the cocci may increase in 



STREPTOCOCCUS PYOGENES. 



565 



very large numbers in tlie marrow tissue (Fig. 425, a, b), and here give 
rise in the first place to tissue-necrosis, and later to a purulent inflam- 
mation of the neighboring tissues. 

A streptococcus infection may terminate, either sooner or later, in 
that the opposing forces of the organism restrict the further spread of 
the bacteria, and destroy them. Not infrequently, however, the infec- 
tion progresses up to the time of death. 

If the streptococci break into the lymph- and blood-vessels, metas- 
tases are often formed, and distant organs are in this way involved. 
Infection of the lungs leads easily to infection of the pleura. Infection 
of the female genital tract, which easily takes place during delivery and 
the puerperium, leads very often to a spread of the infection to the jj^-z i- 
toneum by means of the lymphatics. Infection of the serous membranes 
lead usually to a seropurulent, or fibrinopurulent exudation, the strepto- 
cocci developing luxuriantly in the free exudate, and forming long- 
chains. In infection of the blood, the streptococci do not increase in the 
circulating blood, but at the points where they come to rest ; in the small 
capillaries of the lungs, heart, liver, kidneys, spleen, bone-marrow, joints, 
etc., or even on the valves of the heart. At the point of increase there 
is likewise produced an inflammation, w^hich in general bears the same 
character as the primary inflammation, but is not infrequently less severe 
and more circumscribed. 

Hcematogenous streptococcus-infection of the lung leads to the formation 
of inflammatory foci (Fig. 426, «)» which for the greater part show a 




c 



FIG. 425.— Streptococcus infection of the petrous portion of the temporal bone, from a child of eight 
months of age (foimalin, niti'ic-acid decalciflcation, carmine, methyl-violet), a. Medullary spaces com- 
pletely tilled with sti eptococci ; }>. besrinning invasion by streptococci ; c, bone marrow ; c?, trabeculae of 
bone. X 3U0. 

central suppuration. Collections of streptococci on the surface of the 
endocardium of the valves or of the heart-wall (Fig. 427, a) lead to a 
superficial necrosis and further to the formation of coagula (b), collec- 



566 



THE PATHOGENIC FISSIOX-FUNGI. 



tious of leucocytes (h^) and proliferations of grauulatiou tissue (c, d). 
A deeper infection with the streptococci causes an extensive necrosis of 
the tissue accompanied by an inflanimation of the surrounding tissues. 
If streptococci are carried by the blood stream into the coronary arteries, 
tliere are produced in the heart-muscle inilammatory foci, which are 
usually purulent in character. 

If the cocci pass to a blood-vessel of the skin or subcutaneous tissue, 
they may increase in the same to such an extent that they form perfect 
casts of the capillaries (Fig. 428, c). As the result of the surrounding 
hypercTmia there are produced in the skin red spots and swellings, and 
eventually i^urulent foci. In the I'idneys, in whose vessels there often 
occurs an extraordinary multiplication of streptococci (Fig. 429, a, b), 



a 




Fig. 4:26.— Metastatic ha?mat(igenous streptococcus pneuir.miia, after angina (alcohol, alum-carmine, 
methvl-violet. iodine), a, Pneumonic focus with iblue) streptococci; slitrbtlv inflamed luntr tissue about 
the focus. X yO. 

there arise in the first place grayish-yellow circumscribed areas of dis- 
coloration, which are dependent upon the collection of bacteria, the local 
anaemia, tissue- necrosis, and often a beginning serofibrinous exudation 
(d). Later, yellow discolorations and softening of tissue appear, corre- 
sponding to suppuration. Similar changes may be demonstrated also in 
other organs. 

The danger of a streptococcus infection depends partly upon the severe 
progressive Jocal changes and the formation of metastases, and partly u^^on 
the accompanying intoxication hy toxins (toxaJbumins), which finds expres- 
sion in the fever and the severe general symptoms. If the symptoms of 
intoxication are very prominent the condition is designated septicfemia. 
A predominance of metastatic suppuration leads to the form of disease 
designated as pyaemia. A combination of both conditions is known as 
septicopyeemia or pyosepthaemia {ef. § 12). 



STREPTOCOCCUS PYOGENES. 



567 



The course of a sti^eptococcus infection, as well as the mode of en- 
trance of the cocci into the body, can nsnallj^ be recognized, since the 
infection ordinarily starts in the injured outer skin or from deeply pene- 




FlG. 427.— Endocarditis of till' wall of the I^ft auriclt^. due to streptncocci ^alcohol, metliyl-violet, car- 
mine), o, Masses of coeei ; //. /<i, Jeueocytes and coaji'ula ; c, area of prollferatiou ; </, inflamed endo- 
cardium. X lUU. 




Fig. 428.— Erythema multiforme, due to streptococcus infection, arising in the middle ear (Fig. 425), 
from a child eight mouths old. Section through a red spot in the skin of the back of the foot (alcohol, 
methyl-violet, carmine), a, Corium; 5, subcutaneous tissue ; c, capillaries filled with streptococci. X 46. 



568 



THE PATHOGENIC FISSION-FUNGI. 



tratiiig wounds, from the mucosa of the upper digestive and respiratory 
ti acrs, oi from the genital apparatus as the result of changes due to child- 
birth. Cryptogenic infection is, however, uot rare; in such cases the 
tirst symptoms recognizable or at least uoticed clinically are those de- 
pendent upon the disease of an internal organ, so that it appears as if 
the infection was primary in this organ. 

The individual foci of disease in streptococcus infection may present 
veiy different degrees of severity of inflammation ; and this is dependent 
partly upon the virulence of the bacteria, partly upon the individual 
differences of the infected persons, partly upon the seat of the infection, 



4 



a 




Fig. 429.— Extreme streptococcus infection of tlie kidnnyv fsfrayisli areas), ai ising after streptococcus 
anj^ina (alcohol, Weigerfs stain), a, Cocci in the iutei tubularV iu tue glouieruiar capillaries ; c, urinary 
tubules ; d, fibrin iu the urinary tubules. X 280. 



and partly upor the influence of preceding or accompanying pathological 
conditions. As regards this last factor it may be noted that many infec- 
tious diseases (diphtheria, scarlatina, tuberculosis, typhoid fever, influ- 
enza) which loAver the body resistance increase the predisposition to 
streptococcus infection. In the case of the growth of streptococci upon 
the surface of the endocardium, the inflammation often bears a very pro- 
nounced proliferative character (Fig. 427, d, c). In hiematogenous 
streptococcus-dermatitis (Fig. 428) the process may cease with the for- 
mation of red spots. Phlegmons, which usually run a rapid course and 
lead in a short time to tissue-necrosis and suppuration may (Eeclus, 
Kusnetzoff, Krause, Chiari) also have a very chronic course, particularly 
in the neck, and are then charactei'ized by a progressive swelling and 
induration of the affected area, so that the affection may be designated a 
wooden pldegmon^^ (Keclus). Fever may be wholly absent. The proc- 



STREPTOCOCCUS PYOGENES. 



569 



ess consists of a progressive proliferation of grannlation tissue and a new- 
formation of connective tissue due to streptococci (or staphylococci^, 
while suppuration is absent or confined to circumscribed areas. 

The biological cliaracteristics of the Streptococcus pyogenes are very variable, and 
this is well shown both in its behavior as a disease-producing agent and in the cultures 
of streptococci taken from different cases. Consequently an effort has been made to 
divide the streptococci into ditlerent species, and in particular has the streptococcus 
which causes erysipelas been regarded as a distinct form— the Streptococcus erysipelatis. 
Further, according to the place in which the streptococcus was found, it was formerlv 
customary to speak of a Streptococcus puerperalis (Arloing), Str. articulorum {Flagge), 
Str. scurlatiriostts (Klein); or, according to the manner of growth, of a Str. longus and 
Str. brei'is, etc. {con Liiigelsheirn). These characteristics are, however, not suthcient to 
form a basis for the separation of the streptococci into different sjiecies; and it appears 
more correct, or at least more expedient, to consider all the chain-forming streptococci 
as one species, which appears in many varieties. 

In diphtheria and scarlet fever, streptococcus infections of the throat and air-pas- 
sages are extremely common, particularly in the case of the first named, so that many 
authors {Bnumgarten, Dcilimer) are inclined to assign to the streptococcus a co-ordinate 
pixsition with the diphtheria-bacillus in the causation of diphtheria — the diphtheiia- 
bacilli predominating in the lighter forms of infection, the streptococci in the more 
severe. Pure streptococcus infections may present the same picture as that produced 
by the Loffler's bacillus. If both forms of bacteria are present, their effects may be 
combined; perhaps also the presence of streptococci increases the virulence of the 
diphtheria-bacilli. 

Literature. 

(Streptococcus Pyogenes. ) 

Babes: Siir les streptocoques. Ann. de I'lnst. d. path, de Bucarest, vi., 1898. 
Bender: Ueber den Erysipelcoccus. Cbl. f. Bakt., iv.. 1888 (Lit.). 
Bonome et Bombicci:' Proteine degli streptococchi. Bif. 3Ied., 1899. 
Bordet: Serum autistreptococcique. Ann. de I'lnst. Pasteur, 1897. 
Brunner: Die Begrilfe Pyamie u. Septliiimie, Frauenfeld, 1899. 
Bumm: Die puerperale Wundinfection. Cbl. f. Bakt., ii.. 1887. 
Chiari: Holzphlegnioue. Beitr. z. Dermat., Festschr. f. Neumann, Wien, 1900. 
Dahmer: Streptokokken bei Diphtheric. Arb. her. v. Baumgarten, ii., 1896. 
Dennig-: Septische Infection. Mlinch. med. Woch., 1897. 
Denys: Trav. exec, sur le streptocoque pyog. Cbl. f. Bakt., xxiv., 1898. 
V. Dungern: Mischinfection bei Diphtheric. Beitr. v. Ziegler, xxi.. 1897. 
Fehleisen: Deutsch. Zeitschr. f. Chir., xvi. ; Die Aetiologie des Erysipels, Berlin. 1883. 
Frankel, E.: Identitiit d. Streptococcus pvog. u. Streptoc. erysipelatis. Cbl. f. 
Bakt., vi., 1889. 

Guarnieri: Contrib. alio studio dello streptococco dell' eresipela. Aich. p. le Sc. 
Med., xi., 1887. 

Hajek: Ueb. d. atiol. Yerhaltniss d. Erysipels zur Phlegmone. Wien. med. Jahrb., 
1887. 

HofFa: Ervsipelkokken b. einer Kniegelenksentziindung nach Erysipel. F. d. Med., 
iv., 1886. 

Homen: Die Wirkung d. Streptokokken u. ihre Toxine. Beitr. v. Ziegler. xxv., 1899, 
Howard and Perkins : Streptococcus mucosus. Jour, of Med. Res., 1901. 
Janowsky : Die Ursachen der Eiterung. Beitr. v. Ziegler, xv., 1894 (Lit.). 
Jordan: Die Aetiologie des Erysipels. Arch. f. klin. Chir., 42 Bd., 1891. 
V. Kahlden: Yerhaltn. d. Bakteriolog. z. Cliirurg. Cbl. f. Bakt., i., 1887; Sepsis. 

Eulenburir's Realencvklop., 1899. 
Kusnetzoff: Holzphlegmone. Arch. f. klin. Chir., 58 Bd.,1899. 
Koch: Wundinfectionskrankheiten, Leipzig, 1878. 

Koch u. Petruschky: Erj^sipelimpfungen. Zeit. f. Hyg., xxiii., 1896. 

Krause: Holzart. Entzund d. Bindegewebes. Cbl. f. Chir., 1899. 

Kurth: Unterscheidung der Streptokokken. Arb. a. d. K. Gesundheitsamt, vii., 1891. 

Laitinen: Streptococcustoxin. Cbl. f. allg. Path., vii., 1896. 

X.emoine: Angines non diphtheriques. Ann. de ITnst. Pasteur, ix., 1895. 

V. Lingelsheiin: Eigenschaften versch. Streptokokken. Zeit. f. Hj^g., x., 1891. 

liOngcope ; Streptococcus mucosus (Howard). Jour. of. Med. Res., 1902. 

liubarsch: Streptokokkengruppe. Ergebn. d. allg. Path., iii., 1897. 



570 



THE PATHOGEXIC FISSIOX-FU XGI. 



Lukkomsky : ^Unters. iilier Ervsipel. Yirch. Arch., GOBd.. 1ST4. 
de Marbaix: Et. ^^ur la viruk'uce des streptocoqiies. La Cellule, viii., 1892. 
Marchand : T,a ]iliagocytose des stieptocoques. Arch, de nied. exp.. 1898. 
Marmorek: WtsucTi einer Tlieoiie der septisehrii Kiaukheiieii. Stuttgart. 1894. 
Metsclinikoff : Uebcr deu Kampf der Zelleu gegcudic Ervsipelkokkeu. Vircb. Arch., 

V, Noorden: Sirt^ptokokkc-n iui Blut bci Erysipelas. ^^Iimcli. med. Woch., 18^7. 
Pasquale: Vurglcich. Enters, iilier Streptokokken. B^'iti-. v. Zirgler, xii.. 1893. 
Pawlowsky: Aetiologie tk r aeutcn Peritonitis. Cbl f. Chir., 1887; Ueber die Mikro- 

organisnien des Erysiptds. Berl. klin. Woch.. 1888. 
Petruschky: Ueber die Specifitiit des Ervsipel-Streptococcus. Zeit. f. Hvg., xxiii., 

L896. 

Reclus: Phlegmone ligneux du ecu. Rev. de Chir., 1896. 

Roger: C<'nti\ a ket. exp. du streptocoque de kerysiptle. Rev. de med., 1892, 1896. 
Rosenbach,: Die Mikroorganisnien tkr W undinteetii inskrankheiteu, AViesbaden, 1884. 
Singer: Actiologie ii. Klinik d. acuteu Gelenkrheunia.ismus. Wieu. 1897. 
Vossius: Streptokokkenembolie ini Auge. Zeit. f. Gebh., xviii.. 1890. 
Weaver: The Vitality of Bacteria from the Throats of Scarkt-Fever Patients, with 

Special Study of Streptococci. Jour, of 3Ied. Bes., 11-03. 
Weiss: Aetiologie d. Otitis Media im Silugliugsalter. Beitr. v. Ziegler, xxvii.. 1900. 

§ 153. The Diplococcus pneumonis (Fraiikel, Weichselbaum), or 
Streptococcus lanceolatus (Gamaleia), or Diplococcus lanceolatus ( Foa, 
Bordoni-Uffrediizzi), and also known as the F/ieumocorcus, is a pathogenic 
streptococcus of very frequent occurrence. It forms spherical, oval, and 
lanceolate cocci (Fig. 430, a), which in the human body are usually sur- 
rounded by a transparent capsule, and are grouped together in pairs 
or more rarely in chains of such pairs (c), or in large colonies (d). 
The Diplococcus pneumoniae stains well with fuchsin and with gentian 
violet, and by these stains the capsule may be demonstrated in smear- 
preparations. The cocci are also stained by 
Gram's method. 

The cocci are facultative anaerobes. They 
will not grow upon gelatin at ordinary room- 
temperature, but do so upon slightly alkaline 
blood-serum-gelatin. upon agar and in bouillon, 
at a temperature above 22" C and best at the 
temperattire of the body. Tliey form upon the 
surface of the medium a delicate, translucent, 
glistening culture, which suggests the dew-like 
deposit of moisture upon a cover-glass (Frankel ) ; 
and consists of diplococci and chain-cocci without 
capsules. The growth is, however, scanty; and 
ea^sily dies out. Upon potatoes the cultures do not thrive. 

The Diplococcus pneumoniae is in a great number of cases (according 
to ^\'eichselbaam in seventy-one per cent.) the cause of the affection of 
the lung known as croupous pneumonia, in which the lung is the seat of an 
acute inflammation which is ushered in by a congestive hypersemia (Fig. 
431, a). In the course of the disease the alveoli over large areas of the 
lung become filled with a coagulated exudate consisting of desquamated 
epithelium, leucocytes, red blood-cells, serous flnid and fibrin (Fig. 195). 
In the normal course of the disease the exudate becomes liquefied and 
absorbed. As has been shown by numerous observations, the Diplococ- 
cus pneumoniae may also cause in the lungs other inflammatory processes 
bearing the character of a catarrhal bronchopneumonia, which is charac- 
terized by the formation of foci of a serocellular exudate. During the 
course of the disease the cocci are found especially in the inflamed 
areas, in the greatest numbers at the beginning of the inflammation; 




Fig. 430.— Diplococcus pneu- 
moui*. (.Weicliselbauin.) a. 
Cocci witbout capsule: 7>, 
single and doable cocci with 
a ffeiaiinous rapsule : c, chain 
of encapsulated cocci ; d, col- 
our of cocci. X 5(X). 



DIPLOCOCCUS PNEUMONIA. 57 1 

they lie in part free in the alveoli (b) and in part clinging to cells (d). 
They are found also in parts of the lung bordeiing ui>on the iuHanied 
area, in the pleura, and under certain conditions also in the pericardium, 
peritoneum, meninges, accessory nasal cavities, cellular tissue of the 
neck, in the mediastinum, submucosa of the soft palate and pharynx, 
and even in the conjunctiva itself (Weichselbaum). In all these places 
they may give rise to inflammatory changes. At times thej may be 
demonstrated in the juice of the spleen, and in the blood, and in preg- 
nant women may pass into the foetus (Viti). Under certain circum- 
stances they may be icidely distributed throughout the body ; and may cause, 
in the meninges, pleurae, pericardium, and peritoneum, fibrinous, sero- 
fibrinous, and at times seropurulent, and fibrinopurulent inflamma- 




FiG. 431.— Dipiococciis pneumonia in early stage (formalin, fuchsin). a, Hyperasmic vessels; b, diplococci ; 
c. cellular exudate ; d, swollen epithelial cells covered with cocci. X 501). 

tions, without giving rise to a pneumonia. Further, they may cause in- 
flammations of the endocardium, kidneys, joints, tubes, endometrium, 
parotid, thyroid, bone-marrow, and periosteum, and these inflammations 
may lead to suppuration. In many cases the mouth and nasoi)harynx 
appear to be the avenue of entrance — in these regions the cocci are 
not infrequently found, even in healthy individuals (Weichselbaum, 
Frankel). Correspondingly, in cerebral and cerebrospinal meningitis 
(Weichselbaum) the maxillary cavities, tympanic cavity, and the eth- 
moid labyrinth often contain exudates with diplococci. They are found 
in the exudates in all the forms above mentioned ; and the gelatinous 
capsule may present a very variable thickness. 

When inoculated into rabbits, guinea-pigs, and mice, the cocci in- 
crease in the form of encapsulated cocci, particularly in the blood and 
serous cavities, and may cause p^ieumonia with bloody serous exudate. 



572 



THE PATHOGENIC FISSION-FUNGI. 



When injected beneath the skin of the labbit's ear (Nenfeld) they also 
prodnce erysipelatous inflammations. Rabbits are especially susceptible, 
as they die with symx)toms of septicaemia in from thirty-six to forty-eight 
hours after subcutaneous inoculation. The injection of jyme cultures 
into the i^leural cavity of rabbits gi\ es rise to a pleuritis, as well as a 
splenization of the lung, in which the parenchyma of the organ is filled 
with a hsemorrhagic serous exudate. 

According to A. Frankel the cocci very easily lose their virulence, 
particularly when cultivated upon milk ; and if it is desired to retain 
their virulence they must, from time to time, be passed through suscep- 
tible animals. Cultivation of the cocci at 42° C. for one to two days 
destroys their virulence. 

The Dipiococcifs pneu7-/io?ri(Bhe\ongs to tliose bacteria whose physiological properties 
are very variable. Fod distinguishes, according to the principal places in which they 
are found, a j)ncuinococcus and a meningococcus. In cerebrospinal meningitis cocci are 
found which are closely I'elaled in part to the Streptococcus pyogenes {Streptorocciis 
meningitidis, Bonome), and in part to the Diplococcus pneumoniae (Diplococcus intracel- 
lularis meningitidis, Weichselbdiini). Whether these represent especial forms or only 
varieties of the species mentioned has not at the present time been decided with cer- 
tainty. Jdger is of the opinion that the Diplococcus intraceliularis meningitidis is 
the cause of epidemic cerebrospinal meningitis, and is entirely distinct from the jjneunio- 
coccus. Sporadic meningitis may, on the other hand, be caused also by the pueumo- 
coccus. 

According to Emmerich, there is formed in bouillon-cultures of pneumococci a sedi- 
ment, wdiich contains resistant cells which remain capable of development for montiis. 
Rabbits may be made complete!}^ immune {Emmerich) by repeated injections of highly 
diluted (tive hundred fold) cultures of increasing virulence, so that 30 c.c. of cultures 
of full vii'ulence may be borne Avithout any striking disturbance. The injected bacteria 
die in the course of a few days. The serum of immunized rabbits can cure pneumo- 
coccus infections in rabbits and mice. 

Literature. 

{Diplococcus Fneiimonice.) 

Banti: Contrib. alio studio degli pneumococclii. Lo Sperimentale, 1886; Sull' eti- 

ologia della pneumonite acuta. lb., 1890; Aetiologie der Endocarditis. Deut. 

med. AYoch., 1888; Localisazzioni extrapolmonari del diplococco lanceolato. Arch. 

di Anat., v., Firenze, 1891. 
Emmerich: Infection u. Immunisirung bei croup, pneumonic. Zeit. f. 11}' 2:., xvii., 

1894. 

Faulhaber: Bakterien in d. Kieren bei acut. Infectionskrankheiten. Beit. v. Ziegler, 
X., 1891. 

Foa; Sulla infez. del diplococco lanceolato. Arch. p. le Sc. Med,, xvii. ; Zeit. f. Hyg., 
xiv., 1893. 

Foa u. Bordoni-Uffreduzzi : Bakterienbefunde bei INIeningitis cerebrospinalis. Deut. 
med. AVocli., 1886; Aetiologie d. Meningitis cerebrospinalis epidemica. Zeit. f. 
Hyg., iv., 1888. 

Frankel, A.: Yerh. d. med. Congresses, Wiesbaden, 1884. Zeit. f. klin. Med., x., xi. ; 

Deut. med. Woch., 1886. 
Gabbi: Sull' artrite sperimentale da viro pneumonico. Lo Sperimentale, 1890. 
Gamaleia: Sur I'etiologie de la pneumonic tibrineuse. Ann. de ITnst. Pasteur, ii., 

1888. 

Haeg-ler: Die pvogenen Eigenschaften von Pneumokokken. Fortschr. d. IMed., viii., 

1890. • ^ . " 
Hauser: Pneumoniekokken bei Meningitis cerebrospinalis. Miinch. med. Woch., 1888. 
Herrick: Pneumococcic Arthritis. Amer. Jour, of Med. Sc., 1902. 
Jag-er: Aetiol. d. Meningitis cerebrospin. epidemica. Zeit. f. Hvg., xix., 1896; Deut 

med. Woch., 1899. 
Janowsky: Ursachen der Eiterung. Beitr. v. Ziegler, xv., 1894. 
Koch: Mitrheil. a. d. K. Gesundheitsamte, Berlin, 1881. 

Kruse u. Pansini: Unters. lib. Diplococcus pneum. Zeit. f. Hj^g., xi., 1892. 
Macaigne et Chipault: Aithrites a pneumocoques. Revue de med., 1891. 



STAPHYLOCOCCUS PYOGENES AUREUS. 



573 



Monti: SulT etioloo-ia della polmonite fibriuosa. La Riforma med., iv., 1888. 
Netter: Kech. bactenologi(]nes sur les otites moyennes aigues. Cbl. f. Bakt., v., 1889; 

Le pneiimocoqne. Arch, de med. exp., ii., i890. 
Neufeld: Erzeiigimg v. Erysipel am Kauinchenolir durcb PDeumo-kokken. Zeit. f. 

H> o-.. 36 Bd., 1901. 

Nikiforoff: Ueb. e. dem Pneumococcus ahulicben Mikroorganismus. Zeit. f. Hyg., 
viii., 1890. 

Ortmann: Aetiologie d. acuteu Cerebrospinalmeningitis. Arch. f. exD. Path., xxiv., 
1888. 

Ortmann u. Samter: Localisation d. Diplococcus pneumouife. Yirch. Arch., 120 
Bd., 1890. 

Pipping: Kapselkokken bei Bronchopneumonie. Fortscbr. d. Med., iv., 1886. 
Schabad: Allgemeine Pneiimokokkeninfection. Cbl. f. Bakt,, xix., 1896 (Lit.). 
Seng-er: Bakt. Unters. lib. die Pneiimonie. Arch. f. exp. Path., xx., 1886. 
Tschistovitcli : Et. siir la pneumonie tibrineuse, Ann. de I'lnst. Pasteur, iv., 1890, 
v., 1891. 

Thue: Pleiiritis u. Pericarditis bei der crouposen Pneumonie. Cbl. f. Bakt., v., 1889. 
Viti: Contrib. alio studio dell' infezione pneumonica congenita. Rif. med,, 1890. 




Fig. 433.— Multiple abscesses of the skin, due to stap'^ylooocci (alcohol, carmine. Gram's method). Child 
of three weeks, a, Epithelium ; h, corluiii ; c, hair-follicle ; d, e, purulent foci with cocci. X 40. 

"Weichselbaum : Aetiologie der acuten Lungen- und Rippenfellentzundungen. Med. 
Jahrb., Wien, 1886; Histor. Bericht lib. die Aetiologie der acuten Lungen- und 
Rippenfellentzundungen. Cbl. f. Bakt., i., 1887; Aetiologie d. acuten Meningitis 
cerebrospinalis. Fortschr. d. Med., v., 1887; Aetiologie u. path. Anatomic der 
Endocarditis. Beitr. v. Ziegler, iv., 1888; Seltenere Localisation des pneumonischen 
Virus. Wien. klin. Woch., 1888; Der Diplococcus pneumoniae als Ursache der 
primaren acuten Peritonitis. Cbl. f. Bakt., v., 1889. 

Williamson: Verb. d. Pneumokokkenerkrankung der Kaninchen. Beitr. v. Ziegler, 
xxix., 1901. 

Zaufal: Acute Mittelohrentziindung. Prag. med. Woch., 1889. 

§ 154. The Staphylococcus pyogenes aureus (Eosenbach) or nicro= 
coccus pyogenes (Lehmann) consists of spherical cells occurring singly 
or in pairs, and hy their multiplication forming grape-like clusters and 
swarms. The cocci are easily stained by various aniline dyes, and also 
by Gram's method. They are facultative anaerobes, but gro^^ better 
when supplied with oxygen. 

The staphylococcus thrives on all culture-media, even at ordinary 
room -temperatures, though better at 37° C. It forms white colonies, 



574 



THE PATHOGENIC FISSION-FUNGI. 



wliich produce iTi.uiut^iiT in iliuse parts t-xposed to the air and become 
orange-yellow. The jngnient-forniation is most marked on agar and 
potatoes. Gelatin is slowly li(|uetied. In the i^resence of grai^e-sugar 
it forms lactic ac-id. acetic arid, and valerianic acid. In V)onillon-ciilt- 
ttres there are })r(tdiietMl })mi>. )]]s ^ji very ^nulent action. The Staphylo- 
coccus pyeigene> is one el' the niest frequently occurring pathogenic bac- 
teria, and is. with the Streptococcus pyogenes, the most common cause of 
suppuration. Buth fnrtjrs of cocci are therefore designated pus=cocci, 
in the narrower sense uf the term. It is widely di.stributed throughout 
the external world, and has been demon. strated in milk, wash -water, and 
waste-water, as well as in the air o;[)eratiitg-rooms and sick-chambers. 
Increasing in the tissues r.t the human body (Figs. 432, 433) it causes 
tissue-clf'f/eneratious mid ti-^-siu - /it c/ u-sts \Fig. 434. />^i followed hy (nlfarnma- 
tion (Figs. 432, d, e: 433. Ik c: 434, d, e), whieh is nstially in 
charactw. Imi not infrequently is less severe — tliat is. it doe-'s not lead to 
tissue-xiippiu'(itinit. 

The siippij riitnyii.s prddiieed by staphylococci are tistially cii-cumscrihed 
(Fig. 4o2. 433 . and show a less teiideney to involve rapidly the sur- 
rounding tissue than do the suppurations catised by streptococci. In the 
skin they give lise in xjarticular to the forms of iuHammation known as 




Fig. i.33.— Miliarv purulent nephritis, caused by staphylococci, primary focus in skin (funtnculosisi (alco 
hoL methyl-violet, carmine i . a. Normal kidney tissue : h. collections of cocci : c. purulent focus, x id. 



acne, eczema. fui'uncJe. and cutaneous and subcutaneous abscesses. In the 
osseous system they are the most freqttent cause of the hcematogenous 
purulent diseases uf the bone-marrow and periosteum known as septic 
ostf ninyditis and periostitis. They not infrequently cause j;z^rz//e/;f inHani- 
/nations of the lirer (Fiii. 434 . 7"////.s-, idmrti. pn'iioiu-uni. brain, meninges, 
muscJe, myocardium. spJtt /i. kid/i^i/s, jnints, ete. ; and are often the cause of 



STAPHYLOCOCCUS PYOGENES AUREUS. 



575 



severe, in part purulent, inflmnmations of the endocardium. Since the 
virulence of the staphj lococci varies, thej' can also produce, in all the 
regions named, lighter transitory inflammations which heal with or without 
scar-formation. 

The portal of entrance of staphylococci is often easily recognizable 
(especially in the case of wounds), and the same is true of the path of 



e-'- 




Fi«. 434.— Metastatic collection of staphylococcus in the liver (alcohol. Gram's, vesuvin). a, Normal 
liver-lobules; ?>, necrotic liver-lobules: c, c,. capillaries and veins filled with staphylococci; d, periportal 
small-celled infiltration; e, collection of small round cells, partly within, partly outside a vein, into which 
a centriil vein filled with staphylococci empties. X 40. 



the metastasis to the internal organs, whereby inflammations of the lymph- 
vessels (lymphangoitis) and of the Nood- vessels (phlebitis, aiieritis) make 
their appearance. Cryptogenic infections are, however, of not infre- 
quent occurrence, so that the tirst recognizable localization of the infec- 
tion appears in the endocardium, myocardium, or bone-marrow. The 
spread of staphylococci through the blood-stream leads to multiple locali- 
zation with abscess formation, and this condition is designated pyaemia, 
as in the case of the similar condition caused by the streptococcus. The 
complication of a staphylococcus infection with severe symptoms of 
intoxication is also known as septicaemia ; and the combination of a 
staphylococcus-pv^emia with septicaemia is also known assepticopyaemia 
(cf. g 12). 

The Staphylococcus pyogenes aureus is cdso pathogenic for animals: horse, 
dog, cattle, goat, sheep, rabbit, guinea-pig, and mouse, particularly for 



576 



THE PATHOGENIC FISSION-FUNGI. 



the first-named, less so for the last. In these animals it causes suppu- 
ration. The staphylococcus loses its virulence easilj^ in cultures. The 
inoculation of cultures of high virulence into susceptible animals causes 
a gelatinous oedema. 

Closely related to the Staphylococcus pyogenes aureus are the Staphy= 
lococcus pyogenes albus (Rosenbach) and the Staphylococcus pyogenes 
citreus (Passet) ; these forms probably represent modified varieties of 
the aureus. The albus forms whitish, the citreus lemon-yellow colonies. 
These bacteria occur in the same regions and produce the same effects as 
the aureus, but are more rare than the last named. 

The Staphylococcus pyogenes aureus usually occurs alone in the pus- 
foci, but not infrequently there may be associated with it other pus- 
cocci or even bacilli, as, for example, the Bacterium coli commune, or 
the typhoid-bacillus. 

Literature. 

(Staphylococcus Pyogenes Aureus.) 

Babes: Bakt. Unters. lib. septisclie Processe im Kindesalter, Leipzig, 1889. 
Eockhart: Aetiol. d. Impetigo, d. Furunkels u. d. Sykosis. Monatsb. f. pr. Dermat., 
1887. 

Bonome: Stapbylocoqiies pj^ogenes. Arcb. ital. debiok, viii., 1887. 

de Cb.ristmas: Eeeb. exper. siir la suppuration. Ann. de Tlnst. Pasteur, ii., 1888. 

Deiinig: Ueber septiscbe Erkrankuugen, Leipzig. 1891. 

Escherich: Staobvlokokken in Hautabscessen v. Sau2;bna-en. Miincb. med. AVocb.. 
1886. 

Gainaleia: Les poisons bacteriens, Paris, 1892. 

Garre: Zur Aetiologie der acuten eiterigen Entzlindung. Fortschr. d. ]\[ed.. iii., 1385, 
Heiberg: Die imerperak-n septiscben Processe, Leipzig, 1873. 
Hessler: Die otogene Pyamie, Jena. 1896. 

Kohnfeldt: Ilisiogenese d. durch Stapbvlococcus liervorger. Abscesse. Beit. v. Zieg- 
ler. iii., 1888. 

Janowski-. Die Ursaclien der Eiterung. Beitr. v. Ziegler, xv., 1894 (Lit.). 
Jiirgensen. Kryptogenetische Septikopyamie. Lebrb. d. spec. Patb., Leipzig, 1894, 
V. Kahlden: Sepsis. Eulenburg's Realencykk)p. . 1899. 
Koch: Die Wundinfectionskrankbeiten, Leipzig. 1878. 

Kocher: Osteoinyeli:i-, Periostitis. Strumitis. Langenbeck's Arcb., xxiii.. 1879. 
Kraske; Aetiologie d. ;:euteu Osteomyelitis. A'erb. d. XV. Cbir. -Congr. . Beilin. 1886, 
Krause: Mikrokokken der infectiosen Osteomyelitis. Foitscbv. d. ^led., ii., 1884. 
Liibbert: Der 8'tapbylococcus pyogenes aureus, AVdrzburg, 18S6. 
Neuma,iiii: Micrococcus pyog. tenuis u. Pneumouiecoccus. Cbl. f. Bakt.. vii., 1890. 
Ogston: 3Iicrococcus poisoning. Jouin. of Anat. and Pbys., xvi.. xvii.. 1882. 
Passet: Aetiologie d. acuten eiterigen Entzundung. Fortscbr. d. Med., iii., 1885. 
Petruschky: Infection mit pyogenen Kokken. Zeit. f. Hyg., xvii., 1894. 
Ribbert: Experiment. ]\[yo- u. Endocarditis. Fortschr. d. Med., iv., 1886: Yerlauf 

der durcb Stapbylococcus in d. Haut v. Kanincben bervorgerufenen Entziindim- 

gen. Deut. med. AVocb., 1889; Die patbolog. Anat. u. die Heilung der durcb d. 

Stapbylococcus pyog. aureus bervorger. Veranderungen, Bonn, 189L 
Rodet et Oourmont :' Subst. toxiques elab. par le stapTivloc. pyog. Rev. de med., 

xiii.. 1893 

Kosenbach. Mikroorganismen d, Wundinfectionskrankb., Wiesbaden, 1884. 
SaMi: Aetiol d Gelenkrbeumatismus (Stapb. citreus). Corr. f. Scbweiz. Aerzte, 
1892. 

Scholtz: Paras. Natur d. Ekzems. Deut. med. AVocb., 1900. 

Singer: Aetiologie u. klin. d. acuten Gelenkrbeumatismus, Wien, 1897. 

Steinhaus: Aetiologie d. Eiterung. Zeit. f. Hyg., v., 1888. 

Struck u. Becker: Mikrok. d. infectiosen Osteomyelitis. Deut. med. Wocb., 1883. 
XJllmanii: Fundorte d. Stapbylokokken. Zeitscbr. f. Hyg.. iv., 1888. 
Wyssokowitsch u. Orth: Beitr. z. Lebre v. d. Endocarditis. Vircb. Arcb., 103 Bd., 
1886. 



§ 155. The ilicrococcus Gonorrhcese or Gonococcus (Fig. 435) is a 



GONOCOCCUS. 



57T 



coccus first described by IS^eisser iu the year 1879. It is constantly pres- 
ent in the discharges of the purulent catarrh, known as gonorrhoea, of 
the male and female urethra, and female genital canal (especially of the 
uterus), as well as in the secretions of 
gonorrhceal ophthalmia. It is regarded 
as the cause of gonorrhoea as well as of _ „ c„. 

the blennorrhoea of the eye. Besides the s**- ; ''\ \ ^ 

specific cocci, other cocci may also be 
present in the gonorrhceal secretions, some ' ' * 

of them closely resembling the gonococcus ; 
the pus-cocci may also be present. *^ 

The gonococcus may be cultivated a c 

upon coagulated human blood - serum, ^ 

blood-serum gelatin, on human blood-ser- 
um-agar, on urine-agar ; and forms on the 
surface of the nutrient medium a thin 
grayish-yellow layer having a smooth sur- 
face. It dies out easily, and grows only 

at higher temperatures. Wassermann recommends as culture -medium 
swines' -serum with the addition of glycerin and soda. The cell of the 
gonococcus contains a poison (Wassermann) which, when injected into 
the tissues, excites inflammation. 

Animals are immune against inoculations with the gonococcus. Ef- 



FiG. 435.— Gonococci in the urethral se- 
cretion from a fresh case of gonorrhoea 
(methylene-blue, eosin). a. Mucus with 
single cocci and diplocoeci; b, pus-cells 
with, c, pus-cells without diplocoeci. X 
TOO. 




Fig. 436.— Urethritis gonorrhoica. Cross-section through the mucous membrane which had been 
thrown into folds (Miiller's fluid, hgematoxylln, eosin). o. Normal connective tissue ; 7), c, inflammatory, 
inflltrated, proliferating connective tissue of the mucosa; rf, infiltrated and desquamating epithelium ; e, 
desquamated epithelial cells and pus-corpuscles. X 100. 



forts were made by Bockhart and Bumm to inoculate human beings with 
artificially cultivated gonococci, and they succeeded in obtaining in this 
way a purulent catarrh of the inoculated mucous membrane. The ex- 
periments of Bumm, in particular, appear to have given in the case of 
two women a positive result. 

In the purulent secretion of the mucous membrane infected with gon- 



578 



THE PATHOGENIC FISSION-FUNGI. 



orrhoea the coccus usually forms clumps, and for the greater j^art appears 
in the form of diplococci, the opposing surfaces of which are tlattened 
(Fig. 435) ; but occurs also in part free («), and in part inclosed within 
cells (ft). It stains easily with aniline dyes, but is decolorized by Gram's 
method. 

The gonococcus penetrates into the epithelial layer of the affected 
mucous membrane, and lies partly between and partly in the epithelial 
cells, and in leucocytes. Only the uppermost layers of the connective 
tissue are infiltrated. The infiltration is most marked in the case of 
cylindrical epithelium, while in the regions covered by squamous epithe- 
lium (fossa navicularis, vagina) the cocci lie more superficially. They 
cause inflammations which bear the character of purulent catarrhs, and 
are associated with a cellular infiltration of the tissue of the mucosa 
(Fig. 436, h, c, d) and with epithelial desquamation. The male and 
female urethra and the adjoining parts of the genital glands and ducts, 
and the urinary passages form the chief seats of localization. According 
to Scholz there occurs, after a three-weeks' duration of the disease in 
the male urethra, a metaplasia of cylindrical cells into stratified squam- 
ous cells, and the secretion decreases after this time. To what extent 
the deeper inflammations so frequently accompanying or following gonor- 
rhoea (peri -urethra! abscesses, prostatitis, epididymitis, vesiculitis, cysti- 
titis, inflammation of the ducts of Bartholin's glands, salpingitis, ovar- 
itis, pelvic peritonitis, arthritis, etc. ) are to be referred to the spread of 
the gonococcus or to what extent to secondary infections by the pus-cocci 
is yet a disputed question. According to the investigations made up to 
the present time there can be no doubt that the gonococcus may become 
widely spread over the surface of the mucous membranes. It has been 
many times demonstrated in inflamed tubes, ovaries, joints, cardiac 
valves, tendon-sheaths, burste, in peri- and parametritic foci of inflam- 
mation, and in peri-urethral abscesses. In these cases it has been re- 
garded as the cause of the inflammation, yet the processes which lead to 
suppuration and even the metastases in distant organs appear to be more 
frequently dependent upon the presence of pus-cocci. 

Gonorrhoeal infection is at the beginning an acute process, but may 
become chronic, and is cured only with great difficulty; since the gono- 
cocci can maintain themselves here and there iu the urethra, tubes, etc., 
for years, and continue to cause inflammation. 

Literature. 

( Gonococcus. ) 

Bockhart: Aetiologie u. Pathologie d. Harnrohrentrippers. Vierteljahrssclir. f. 

Derm., 1883; Secuudilre Infection (Mischinfection) b. Tripper. Monatssclir. f. 

prakt. Derm., 1887. 
Brbse: Diffuse Gonorrhoeal Peritonitis. Berl. klin. Woch., 1896. 

Bumm: Der Mikroorganismus d. gonorrhoischen Schleimhauterkrankungeu, Wiesbad- 
en, 1886. 

de Christmas : Le gonocoque et sa toxine. Ann. de I'lnst. Past., 1897, 1900. 

Gushing. Gonococcus peritonitis. Bull, of the J. Hopkins Hosp., 1899. 

Finger: Die Blennorrhoe d. Sexualorgane u. ihre Complicationen, Leipzig, 1896; Die 

Syphilis und die venerischen Krankheiten, Wien, 1901. 
Finger, Ghon u. Schlagenhaufer : Beitr. z. Biol. d. Gonococcus. Arch. f. Derm., 

xxviii., 1894; Endocarditis, Arthritis, Prostatitis. lb., xxxiii., 1895. 
Fritsch: Die gonorrhoischen Erkrankungen d. weibl. Sexualorgane, Berlin, 1892. 
Ghon u. Schlagenhaufer: Zur Biol. d. Gonococcus. Wien. klin. Woch., 1898. 
Haab, O. : Der Micrococcus der Blenuorrh. ueonat. Horner'sche Festschr., 1881. 



THE PATHOGENIC COCCI. 



579 



Hartdegen: Der Gonococcus Neisser u. s. Bez. zur Gonorrhoe. Cbl. f. Bakt., i., 1887 
(Lit.). 

Heiman: Studies on the Gonococcus, i., ii., iii. series. Studies from Dept. of Path, of 

Columbia University. 
Jadassolin: Path. Anat. d. gonorrh. Processes. Verh. d. derm. Congr,, 1894. 
Krause: Die Mikrokokken der Blennorlioea neonatorum. Cbl. f. Augenheilk., 1882. 
Lang-: Der venerische Katarrh, Wiesbaden, 1893. 

Lartigau: Gonorrhoeal Ulcerative Endocarditis. Amer. Jour, of Med. Sc., 1901. 
Martin: Recli. s. I'intlamm. metastat. suppur. a la suite de la gonorrhee, Geneve, 1882. 
Neisser: Cbl. f. d. med. Wiss.,1879; Deut. med. Woch., 1882; Bresl. arztl. Zeitschr., 

1886; Bedeut. d. Gonokokken f. d. Diagnose. Arch. f. Derm., xxi. Bd., Ergan- 

zungsh., 1889. 

Pelizari: Gonokokken in periurethralen Abscessen. Cbl. f. allg. Path., i., 1890, 
Schaffer: Gonokokken. Ergebn. d. allg. Path., iii., 1897 (Lit.). 
Scholz: Zur Biologic d. Gonococcus. xlrch. f. Derm., 49 Bd., 1899. 
See: Le gonocoque, Paris, 1897. 

Steins chneider : Kultur der Gonokokken. Berl. klin. Woch., 1893. 

Thayer u. Blumer: Endocardite blennorrhagique. Arch, de med. exp., 1895. 

Thayer and Lazear : Gonorrhoeal Septicaemia and Ulcerative Endocarditis, with Ob- 
servations upon the Cardiac Complications of Gonorrhoea. Jour, of Exp. Med., 
1899 (Lit.). 

Touton: Ueber Folliculitis pragputialis et paraurethralis gonorrhoica. Vierteljschr. f. 
Derm., xxv., 1889; Der Gonococcus u. s. Bez. z. Blennorrhoe. Berl. klin. Woch., 
1894. 

Wassermann : Gonokokkenkultur u. Gonokokkengift. Berl. klin. Woch., 1897. 
Wertheim: Die ascendirende Gonorrhoe beim Weibe. Arch. f. Gyn., 42 Bd., 1892. 

§ 156. Cocci have been demonstrated with certainty as the cause of 
disease in animals in the case of a large number of infectious diseases, 
and are regarded with probability as the cause in the case of others. 
As has already been stated, the Streptococcus pyogenes, the Biplococcus 
pneumoniae, and the Micrococcus pyogenes aureus are also pathogenic for 
different animals, and the last named in particular often causes sponta- 
neous — not caused by inoculation — suppurative inflammations in animals. 
Moreover, diseases have also been produced experimentally in animals 
by different cocci which were not pathogenic for man. Further, in 
many spontaneous diseases of animals cocci have been demonstrated, 
which are probably to be regarded as the cause. 

(1) According to Schiitz (" Der Streptococcus der Druse der Pferde," Arch. f. wiss. ii. 
prakt. Thierlieilk., xiv., 1888; Zeit.f. Hygiene, iii.), Sa/idandJensen (" Die Aetiologie der 
Druse," Beutsch. Zeit.f. Thiermed., xiii.), and Poels{''T>\e Mikrokokken der Druse der 
Pferde," Forischr. d. Med., vi.) the strangles of horses is an infectious disease, in which 
the mucous membrane of the upper respiratory tract is the seat of a mucopurulent 
inflammation, in w^hich, moreover, the lymph-glands pertaining to the region become 
swollen and in part suppurate; and is caused by a chain forming coccus, which can be 
cultivated, and, when inoculated into horses {Schiitz) again produces the disease. 

(2) According to Schiitz ('' Die Ursachen der Brustseuche des Pferdes, " Arch. f. wis- 
sensch. ic. prakt. Thierheilk., 1887; Virch. Arch., 107 Bd., 1887) the epide?nic lung-dis- 
ease of horses (infectious pneumonia) is caused by an oval coccus, which forms pairs and 
chains, and is not identical with the Diplococcus pneumoniee (Frankel) or the Bacillus 
pneumoniae (Friedlander), and therefore not identical with the bacterium described by 
Perroncito (Arch. ital. de biol., vii., 1886) as occurring in the pneumonia of horses, and 
held by him to be identical with the Diplococcus pneumoniae. 

(3) According to Semmer and Archangelski {Centralhl. f. d. med. Wiss., 1883; 
Beutsch. Zeit. f. Thiermed., xi.) the microparasite o^ "Rinderpest" is a micrococcus. 
According to Metschnikoff and Gamale'ia {Centralhl. f. Bakt., i., p. 633) it is a bacillus. 
The disease is characterized anatomically by an inflammation of the intestinal tract, in 
part of a croupous or diphtheritic character, as well as by swelling and at times necro- 
sis of Peyer's patches. 

(4) According to Poels and Noleii {Fortsch. der Med., iv., 1886) monococci and diplo- 
cocci, which in part possess a gelatinous capsule, are found constantly in the lungs and 
in the pleural exudate, in the contagious pleuropneumonia of cattle. On gelatin and agar- 



580 



THE PATHOGENIC FISSION-FUNGI. 



agar they form chiefly white colonies which later become cream-colored. Pure cultures 
injected into the lungs of rabbits, guinea-pigs, dogs, and cattle give rise to pneumonic 
changes. (Literature: Pasteur, Reciieil de med. vet., 1883; Cornil et Babes, Arch, de 
pJiys., 1883; Sussdorf, Deut. Zeitsclir. f. Thiermed., 1879). 

(5) In the udder-inflammations of the domestic animals, which occur sometimes 
sporadically, sometimes epidemically, different micrococci and streptococci have been de- 
scribed, and designated by various names (^Hess and Bergeaud, " Contag, Euterentziin- 
dung, gelber Gait genannt," Schweiz. Arch. /. ThierJieilk., 30 Bd., 1888; Frank, "Euter- 
entzilndungen," Dtsch. Zeit. f. Thiermed., ii,, 1876; Kitt, " Euterentziindung," " Lehrb. 
d. path. anat. Diagnostik," Stuttgart, 1894; Jensen, "Mastitis," Ergehn. d. allg. Path., 
iv., 1899). 

(6) According to Johne (" Seuchenart. Cerebrospinalmeningitis d. Pferde," Dtsch. 
Zeitschr.f. Thiermed., xxii., 1887) the cerebrospinal meningitis, which occurs epidemi- 
cally in horses, is caused by the Diplococcus intracellularis (Weichselbaum, § 153). 

(7) Babes found in the liaemoglobinuria of cattle, which occurs as an epidemic 
disease in Roumania, a coccus similar to the gonococcus, which he regards as the cause 
of the disease (''Sur I'hemoglobinurie bacterienne du boeuf," Compt. rend, de I'Acad. des 
Sciences de Paris, cvii., 1888; Virch. Arch., 115 Bd. ; Annal. de V Instiiut de patlwl. d 
Bucarest, 1890). 

(8) According to Semmer, Friedberger, and Mathis {Centralbl. f. Bakt., iii., p. 343) 
the distemper of dogs is also caused by a coccus, 

(9) The foot-and-mouth disease of cattle, according to Klein {GU. f. d. med. Wiss., 
1886) is caused by a streptococcus. Several years ago Schottelius (" Ueber einen bak- 
teriologischen Befund bei Maul- und Klauenseuche," Cbl. f. Bakt., xi., 1892) and Kurth 
("Bakt. Untersuch. bei Maul- und Klauenseuche," a. d. Reichsgesundheitsamt, viii., 
1893), and others also found cocci in the organs of animals affected with foot-and-mouth 
disease ; but the bacteria described do not correspond with one another, and their path- 
ogenic significance is doubtful {Johne, Dtsch. Zeitschr.f. Thiermed., xix., 1893; Loffler 
and Frosch, Cbl. f. Bakt., xxii., p. 257, 1897). 

(10) According to Riwlta and Johne {Dtsch. Zeitschr. f. Thiermed., xii. ; "Bericht 
iiber das Veterinarwesen im Konigr. Sachsen f . d. J. 1885 ") and Babe {Dtsch. Zeitschr. 
f Thiermed., xii.) there occurs in horses a peculiar tumor-like growth of connective tis- 
sue, designated by Johne as mycofihroma or mycodesmoid, which is caused by a micrococ- 
cus that grows in animal tissues in round or grape-like colonies which quickly become 
surrounded by a hyaline capsule, and are therefore to be reckoned as ascococci {Micro- 
coccus ascoformans). Bollinger designates the coccus as Botryomyces, Babes as Micrococ- 
cus botryogenes, Kitt as Botryococcus ascoformans. The growths consist of connective 
tissue, resembling those of actinomycosis, and inclose small suppurating foci of granu- 
lation tissue which contain the fungi. They appear to develop most frequently in the 
spermatic cord after castration, but occur also on other parts of the body {Kitt, " Der 
Micrococcus ascoformans und das Mycofibrom des Pferdes," Cbl. f. Bakt., iii., 1888; 
Schneidemilhl, "Botryomycosis," Cbl.f. Bakt., xxiv., 1898 [Lit.]). 

(11) According to Eberth {Virch. Arch., 80 Bd.) and M. Wolff {Virch. Arch., 92 
Bd.) many of the gray parrots brought to Europe {Psittacus erithacus) die of a strepto- 
coccus mycosis. The micrococci are found in almost all the organs, but especially in 
the capillaries of the liver and their neighborhood, where they cause necrosis of the 
liver-cells, but no suppuration. 

(12) According to Eberth {Virch. Arch., 100 Bd.) a part of the pseudotuberculous 
processes occurring in guinea-pigs represent a chronic suppuration caused by a coccus, 
and sometimes lead to metastases in other organs, 

2. The Bacilli and the Polymorphous Bacteria, and the 
Pathological Processes Produced by Them. 

(a) General Considerations Begarding Bacilli and the Polymorphous Bacteria. 

§ 157. Under the designation bacilli or bacillaceae (A. Fischer), or 
Bacteriacece (Zopf) may be classed all those bacteria which occur in the 
form of straight rods or rods which are slightly bent in one plane. By 
many authors (Oohn, Hiippe, Lehmann) the bacillacese are divided into 
two groups: bacterium and bacillus, the latter being characterized by 
the production of endogenous spores, while spore -formation is lacking 
in the former. 



THE BACILLI. 



581 



The bacilli iiiiiltiply by division. The rods grow in length, and 
divide into approximately eqnal parts through the formation of a trans- 
verse partition -wall. If the division of one of the elongating bacilli is 
delayed, or if the separation of the individual rods from one another is 
not distinctly recognizable, there arise long, unbranched I'ods or threads 
(Fig. 438, h). If the divided rods remain attached to each other, there 
are formed chains of rods (Figs. 437, c; 438, c). In many forms of 
bacilli the ends of the individual rods are blunt, in others rounded or 
pointed. 

In many bacilli resting as well as swarming stages are observed. 
Flagella serve as the organs of motion (Fig. 437, h) ; they are situated 
sometimes at the ends, sometimes on the sides of the rods, and may occur 
in large numbers. In many bacilli an endogenous spore=formatioii is 
observed (Figs. 437, d, e; 438, d), the spores lying sometimes in the 
middle, sometimes at one end of the cell. Not infrequently the spores 
appear within jointed threads. The germination of spores results in the 
formation of new rods (Figs. 437,/'-^ 438 e'-'). 

During spore-formation the rods usually do not change their shape 




1 a 3 *• V 




FIG. 437. FIG. 438. 

Fig. 437.— Bacillus subtilis In various stages of development (Prazmowski). a. Single rods; 7/, rods 
with flagella ; c, chain of rods ; d, single cells v^^ith spores ; e, chain of rods with spores ; / gerinlnation 
of a spore. X 800. 

Fig. 438.— Clostridium butyricum (Prazmowski). «, Short rods ; ?>, long rods ; c, chain of rods ; fi, cells 
with spores ; e ^—''^ germination of a spore. X 800. 

to any marked extent. In other cases they assume a spindle-, club-, or 
pear-shape (Fig. 438, d), and these changes have been taken as the basis 
for the establishment of an especial group, Clostridium. On the other 
hand, numerous authors class these forms with the bacilli. 

In the non-pathogenic bacilli spore -formation and spore-germination 
have been more carefully studied, esj)ecially in the case of Bacillus subtilis 
and Bacillus amylohacter ; and these bacilli offer good examples of the 
processes which come under consideration in this connection. 

Bacillus subtilis is a fission-fungus whose spores are widely distrib- 
uted in the ground, hay (hay-bacillus), and in the air. When cultivated 
ui)on potato or upon the dung of herbivorous animals, it forms whitish- 
yellow colonies; upon liquids it forms thin and thick pellicles. It re- 
quires oxygen for its development. 

The fully developed rods (Fig. 437, a) are 6 long. The snake-like 
motions occurring at times are produced by means of numerous lateral 
and terminal flagella. Through the growth of the rods undivided threads 
are formed which after division form chains of rods. The separate cells 
may develop in their interior glistening, sharply contoured spores ((7, e), 
which lie either in the middle or nearer to one end of the cell. Later 



5S2 



THE PATHOGENIC FISSIOX-FUNGI. 



tlje cells iu which the spoi es have been formed die. During germination 
the spores become pale (Fig. 437 lose their glistening appearance 
and their sharp contour. A shadow then ai^pears at each pole, while the 
spore begins a tremulous motion. After a time the contents of the spore 
project from the membrane of the spore in the form of a germinal utricle, 
which later becomes elongated, divides, and produces swarming rods. 
The empty spore membrane may remain preserved for some time after 
the exit of the young cell. 

The Bacillus butyricus (Bacillus amylobacter of Van Tieghem, Yibrion 
huti/rique of Pasteur, CJostridium l)utij)'icu)}) of Prazmowski) consists of 
rods of 3 to 10 in length, and also forms threads and chains of rods. 
During spore-formation the cells become spindle-, club-, or tadpole- 
shaped (Fig. 438, d), and then jDroduce one to two glistening spores. In 
germination, after the absorption of the spore-membrane a germinal 
utricle appears at one of the two poles (Fig. 438, e'-'); this becomes 
elongated, and produces new rods by segmentation. 

The BaclUus buti/ricus does not need oxygen for its development ; it 
produces butyric-acid fermentation with evolution of carbonic acid, in 
solutions of starch, dextrin, sugar or glycerin. In media containing 
starch, glycerin, or cellulose the bacilli are colored blue with iodine. 

The polymorphous bacteria are distinguished from the bacilli hj the 
fact that they form, besides rods, also long threads, in part with false or 
true branching; and in individual cases a basal non -proliferating end 
and an apical proliferating end may be distinguished. In this category 
may be placed the fungi designated StreptotJuix, Cladothrix, Beggiatoa, and 
Crrnolhrix. They are here placed Avith the bacilli, because, on the one 
hand, their botanical i^osition is not definitely determined, while, on the 
other, in so far as they are pathogenic, they conform most closely to the 
bacilli in their biological properties (cf. diphtheria-bacilli, tubercle- 
bacilli, and actinomyces). 

The saprophytic bacilli produce many forms of fermentation by their 
growth in nutrient fluids; many also form 2)ignients. 

Bacillus prodigiosus grows upon potatoes and bread, as well as upon 
agar-aga]', and upon nutrient gelatin, liquefying the latter. It forms a 
red coloring matter which is soluble in alcohol. The pigment is formed 
only in tlie presence of oxygen ; in the growth in milk the coloring-mat- 
ter is contained in the fat-droplets. The bacilli themselves are always 
colorless. 

Bacillus fluorescens liquefaciens forms whitish cultures in gelatin, 
in the neighborhood of which the gelatin is liquefied while in the remote 
surrounding portions it gradually takes on a greenish-yellow fluorescence. 

Bacillus cj^anogenes (Xeelsen, Hueppe), when cultivated in sterilized 
milk, causes a slate-gray color that changes through the addition of acid 
to an intense blue. In unsterilized milk, in which lactic -acid bacteria 
develop at the same time, a blue color a^Dpears without the addition of 
acid. On potatoes it forms yellowish, slimy cultures, in the neighbor- 
hood of which the substance of the potato is colored grayish-blue 
(Fliigge). 

Bacillus acidi lactici ferments milk-sugar into lactic acid and coagu- 
lates casein. In gelatin it produces white cultures. 

Bacillus caucasicus (Dispora caucasica) forms one of the constituents 
of the fungus-conglomerate known as kephir-ferment, which is used by 
the inhabitants of the Caucasus in the preparation, from cow's milk, of 
the alcoholic drink callecl kephir. The kephir-ferment consists of small 



SAPROPHYTIC AND IN PART PATHOGENIC BACILLI. 583 



granules coutaining yeast-cells and bacilli. The latter at times show 
movements, aud form a round spore at the end of each rod. As the re- 
sult of their growth in milk the milk-sugar is' probably converted into 
glucose, while the yeast-cells produce alcoholic fermentation. According 
to Hueppe, the kephir granules contain still other bacteria which pepto- 
nize casein. 

As Proteus vulgaris, Hauser has described a bacillus {Bacterium vul- 
gate of Lehmann) which is very frequently present in decomposing ani- 
mal substances aud in human cadavers, and in gangrenous ulcers, and 
causes putrid decomposition. It forms rods of varying length, and jDro- 
duces, when cultivated in meat (Carbone), sethylendiamin, gadinin, and 
trimethylamin, of which the first two bases are poisonous for animals. 
According to observations by numerous authors, it is not infrequently 
found in human tissues, chiefly in association with other bacteria, strepto- 
cocci, pneumococci, diphtheria-bacilli; and by its presence aggravates 
the course of the infection and cajuses putrid decomjjositmi of the pus and 
the necrotic tissue. In rare cases it may alone, without the association 
of other bacteria, cause inflammations, particularly of the urinary bladder 
(cystitis). Several cases of hcemorrhagic enteritis have also been described, 
in which a form of proteus was regarded as the causal agent. Further, 
proteus has also been found in inflammations of the female genital tract, 
serous membranes, and liver (infectious icterus), and has been considered 
to be the cause of the given inflammation. Proteus must therefore be 
classed with the parasitic or pathogenic bacteria. Its pathogenic activity 
rests chiefly upon the formation of poisonous substances. (Literature 
given by Me^whof, I. c). 

Bacillus aceticus {Mycoderma aceti) is a bacillus which converts the 
alcohol of fermented beverages into acetic acid. 

Bacillus pyocyaneus occurs occasionally in bandages upon suppurat- 
ing wounds and causes a greenish-blue discoloration of the same. The 
bacilli are small and slender. The cultures show diflerent forms of 
growth. Gelatin is liquefied and turned green. The coloring-matter 
Q,?i\\Q^ pyocyanin is soluble in chloroform and crystallizes from the solution 
in longijlue needles. The bacillus is pathogenic for rabbits, guinea-pigs, 
pigeons, and frogs ; inoculations give rise partly to local ulcerations, partly 
to general infections. According to Kossel, Kramhals, Neumann, and 
others it may also be pathogenic for man during the age of childhood, and 
from suppurating wounds or mucous membranes (middle ear) it may 
cause septicaemia with splenic tumor and enteritis. Blum observed a 
pyocyanic endocarditis in a nursing infant. 

The pathogenic bacilli and polymorphous bacteria cause partly 
acute, and partly chronic affections, the former terminating either in 
death or in healing after the destruction of the bacteria. It also hap- 
pens in the acute diseases that the bacteria may remain in the body for a 
long time. The chronic affections are characterized by the persistence 
and multiplication of the bacteria within the body, so that the disease 
assumes a progressive character, and sometimes slowly, sometimes rapidly, 
new regions are in turn invaded by the bacteria and suffer pathological 
changes. 



684 



THE PATHOGENIC FISSION-FUNGI. 



Literature. 

{Saprophytic [in Fart Pathogenic] Bacilli.) 

Babes: Recb. siir les bacilles du pus vert. Ann. de I'lnst. de path, de Boucarest, i., 
1890. 

Banti: Sopra quatri nuove specie di Protei o Bacilli capsulati, Firenze, 1888. 
Blum: Pyocyaneusseptikamie. Cbl. f. Bakt., xxv., 1899. 
Bordoni-Uffi'eduzzi : Proteus hominis capsulatus. Zeitschr. f. Hyg., iii.,1888, 
Bunge: Geisseltragende Bakterien. Fortschr. d. Med., xii., 1894; Sporenbildung. 
lb., xiii., 1895. 

Carbone: Ueber die von Proteus vulgaris erzeugten Gifte. Cbl. f. Bakt., viii., 1890. 

Ch.arrin: La maladie pyocyanique, Paris, 1889. 

Ernst: Bacillus des blauen Eiters. Zeitschr. f. Hyg., ii., 1887. 

Foa et Bonome: Maladies causees par Proteus. Arch. ital. de biol., vii., 1887. 

Frankel : Ueber Gasphlegmone, Leipzig, 1893. 

Frick: Griines Sputum u, griinen FarbstofE produc. Bacillen. Virch. Arch., 116 Bd., 
1889. 

Gessard: Rech. sur le microbe pyocyanique. Ann. de I'lnst. Pasteur, 1890. 
Goebel: Bacillus d. Schaumorgane. Cbl. f. allg. Path., vi., 1895. 
Gretlie: Keimung d. Bakteriensporen. Fortschr. d. Med., xv., 1897. 
Hauser: Ueb. Faulnissbakterien u. deren Beziehung z. Septikamie. Leipzig, 1885. 
Heim: Versuche liber blaue Milch. Arb. a. d. K. Gesundheitsamte, v., 1890. 
Jaeg-er: Die Aetiologie des infectiosen iieberhaften Ikterus. Zeitschr. f. Hyg., xii., 
1892. 

Jakowsky: Bakterien des blauen Eiters (B. pj^ocyaneus). Zeitschr. f. Hyg., xv., 
1893. 

Kossel: Zur Frage d. Pathooeuitiit des Bac. pyocvaneus. Zeitschr. f. Hyg., xvi., 
1894. 

Kramhals: Pyocyaneusinfectiou. Deut. Zeitschr. f. Chir., 37 Bd., 1893. 

Krause: Zur Keuntn. d. Bac. pyocyaneus. Cbl. f. Bakt., xxvii., 1900. 

Lartigau: Bacillus pyocyaneus"^ as a Pathological Factor. Phil. Med. Jour., 1898. 

Ledderhose: Ueber den blauen Liter. Deut. Zeitschr. f. Chir., xxviii., 1888. 

Levy: Die Aktinomycesgruppe. Cbl. f. Bakt., xxvi., 1899 (Lit.). 

Meyerbof: Biologische u. thierpathogene Eigenschaft des Bacillus proteus (Hauser), 

mit einer Zusammenfassung d. wichtigsten Literatur liber Proteus. Cbl. f. Bakt., 

xxiv., 1898. 

Miller : Die Mikroorganismen der Mundhohle, Leipzig, 1896. 

Prazmowski: Unters. liber d. Entwickelungsgeschiclite einiger Bakterien, Leipzig, 
1880. 

Perkins : Report of Nine Cases of Infection with Bacillus Pyocvaneus. Jour, of Med, 
Research, 1901. 

Schedtler: Beitr. z. Morphologic der Bakterien. Virch. Arch., 108 Bd., 1887. 
Schimmelbusch: Grliner Eiter u, d. Bac. pvocyaneus. Samml. klin. Vortr., No. 62, 
1893. " . 

(h) The Pathogenic BaciUi and PoJymo)phous Bacteria. 

% 158. The Bacillus anthracis {Bacteridie du charbon) is the cause of 
anthrax, a disease occurring chiefly In cattle and sheep, and occasionally 
transmitted to man. It is a fission-fungus which, when inoculated into 
a susceptible animal, may increase within the tissues as weH as in the 
blood. 

The anthrax=bacilli (Fig. 439) are 3 to 10 [j. long and 1 to 1.5 a 
broad. In the blood of animals affected with anthrax they occur either 
singly or in thread-like jointed bands of two to ten rods, whose ends are for 
the greater part sharply cut across (Figs. 439, 440), more rarely slightly 
concave or even slightly convex ( Johne). According to Pianese, Sera- 
fini, Giinther, and Johne they possess a gelatinous capsule which is best 
brought out by the staining of dried preparations with methylene-blue. 
They can be cultivated upon blood-serum-gelatin, in bouillon, upon 



BACILLUS ANTHRACIS. 



685 




Fig. 439.— Section from a liver whose capillaries 
contain numerous antlirax-bacilli and scattered 
leucocytes (alcohol, gentian-violet, vesuvin). X 
300. 



slices of potatoes and turnips, in infusions of peas and mashed grain of 
various kinds, etc., in the presence of oxygen (according to Klett also 
in an atmosphere of nitrogen) ; and grow most rapidly at a temperature 
of from 30° to 40° C. At temperatures below 15° and above 43° C. 
development is impossible. 

Under suitable conditions of growth the rods increase in length, and 
may within a few hours form non-encapsulated threads of considerable 

length. These consist of short seg- 
ments whose outlines may be made 
visible by treatment with iodine or 
by stains (Fig. 440). Ten hours 
later the clear contents of the 
threads become granular, and at 
regular intervals there become ap- 
parent dull-shining bodies, which 
after a few hours enlarge into 
strongly refractive spores (Fig. 
440). Later the threads disinte- 
grate and the spores become free. 

According to Bref eld, Prazmow- 
ski, Klein, and others, the spore 
consist of a protoplasmic centre, 
which is inclosed by a double mem- 
brane, the exosporium and the en- 
dosporium. During germination 
the former is ruptured, the latter 
becomes the membrane of the embryo. The liberated embryo multiplies 
by division. 

Swarming movements are not seen throughout the entire period of 
development ; the bacilli are always motionless. 

The bacilli of anthrax are easily killed by high temperatures, drying, 
and through the decomposition of the nutrient fluid. The spores on the 
other hand are very resistant, and are therefore 
usually the medium of the spread of the disease. 

The colonies upon gelatin show a wavy, ir- 
regularly shaped margin, and consist of many 
interlacing strands of threads, which later grow 
out of the culture in all directions. The gelatin 
is liquefied immediately about the culture. On 
potato the bacillus forms grayish -white, slightly 
granular colonies having a sharply outlined bor- 
der. On blood-serum it forms a white coating. 

Stab -cultures in gelatin are white and during 
the process of growth they radiate at right an- 
gles from the line of inoculation out into the gel- 
atin, particularly near the surface. After liqne- 
faction of the gelatin they sink to the bottom. 

If the bacilli or the spores gain entrance into the blood, they increase 
and form rods as described above, which stain with different aniline 
dyes, and also by Gram's method. Sections of hardened tissue show that 
they are present in large numbers in the capillaries (Fig. 439), particu- 
larly in the spleen, liver, lungs, and kidneys. The neighboring paren- 
chyma for the greater part appears unchanged ; still the local prolifer- 
ation of the bacilli can also cause tissue -degeneration and necrosis. If 



Fig. 440.— Spore - containing 
anthrax-bacilli and free spores. 
Cover-glass preparation from a 
culture of the bacilli grown in 
the incubator upon potato, and 
stained with fuchsin and meth- 
ylene-blue. X 800. 



5S6 



THE PATHOGENIC FISSION-FUNGI. 



an infection of the blood takes place during pregnancy the infection niay 
X)ass over to the foetus. 

Anthrax-bacilli or their spores may gain entrance into the skin of 
man, an event which is particularly likely to happen in the case of indi- 
A'iduals who butcher, or shear, or prepare the skins of animals affected 
with anthrax ; or occasionally the infection may be transmitted by means of 
the sting of a fly which has taken up blood from an animal infected with 
anthrax. There develops at the place of infection a somewhat elevated 
pustule (Fig. 441) from 6 mm. to several centimetres in diameter, hav- 
ing an arched or flattened surface, and of a red or at times a more yel- 
lowish color. This is often after a time covered with vesicles, or after 




Fig. 441.— Section from an antbrax-pustule ten days old, taken from the arm of a man (alcohol, 
Gram's method, vesuvln). a. Epidermis ; h, coriiim ; c, papillary body oedematously swollen and infiltrated 
with exudate and bacilli: d, outer layer of corium, Infiltrated with cells; d], the same, containing also 
bacilli; e, deep layers of the corium infiltrated by cords of ceils; /, dermal tissue infiltrated with bacilli 
and cells ; g, bloody exudate containing bacilli, lying upon the surface ; 7i, hair-follicle ; i, sweat-gland. 
X 33. 

the loss of the epithelium becomes moist ; so that through the drying of 
the oozing, often bloody exudate, a scab is formed (Fig. 441, g). 

The centre may become depressed through the formation of a central 
scab, so that the edges form a wall about the latter. The neighborhood 
of the pustule is sometimes but slightly changed, at other times reddened 
and swollen, and may be set with small yellow or bluish-red vesicles. 
If the process remains local, the gangrenous pustule may be thrown off. 
Infection of the blood is fatal. In rare cases the infection from the 
beginning may show itself as an extensive, intense, cedematous swelling 
of the tissue without the formation of a circumscribed elevation. 

In the region of a fully developed anthrax-pustule (Fig. 441), the 
corium (d, d^) and the papillary body (c) are infiltrated with a serocellular 



BACILLUS ANTHRACIS. 



587 




exudate as well as by bacilli. The bacilli lie particularly in the outer 
portions of the corimn (dj and in the i^apillary body (c), but may also 
penetrate into the deeper layers of the corium (/). In the neighborhood 
of the papillary body (c) the exudate is sanguineous. Vesicles filled 
with bloody fluid result if the exudate extends up to the epithelial cover- 
ing, and if the deeper portions of the latter become liquefied, thereby 
permitting the lifting-ui3 of the superficial layers by the exuded fluid. 
If the upper layers of the skin are also lost, the bloody fluid containing 
the bacilli {//) aj^x^ears upon the surface. 

The cellular infiltration has its seat chiefly in the corium (d, d^, e), 
and the imx^ression is obtained as if the great massing of cells formed a 
certain protection against the further spread ^ .-■^v .,^. 

of the bacilli. The cells which collect belonf ^ '^^^ ■ ^'^-^^ 
for the greater i^art to the poly nuclear leuco- 
cytes (Fig. 442). The bacilli lie sometimes 
in, sometimes between the cells. 

If an infection with anthrax -spores takes 
j)lace in the intestinal canal, an event which 
occurs most frequently in the small intestine, 
less often in the vStomach and large intestine, 
there develop dai-k-red or brownish-red h^em- p^^S^ielfo^^'fhf arm %Tmu 
orrhagic foci, the size of a lentil or bean or containing baciiii. x m 
larger, with a grayish-yellow or greenish-yel- 
low, discolored slough in the centre. In other cases the crests of the 
folds of the mucosa are swollen and h^emorrhagic, and show evidences 
of sloughing in the most prominent j)arts. The mucosa and submucosa 
are infiltrated with blood in the region of the foci ; the surrounding tissues 
are cedematous and hyj)er8emic. Bacilli are found in the tissues both 
in and about the foci, particularly in the blood- and lymph-vessels, and 
they may also be demonstrated in the neighboring lymph-glands. 

According to observations by Ei)i3inger and Paltauf , primary lung in- 
fection may also occur in man as the result of the inhalation of anthrax- 
spores, proving fatal in from two to seven days. Individuals who have to 
handle the hair of animals that have died of anthrax are especially ex- 
posed to infection ; and the disease known as rag-sorter' s disease, which oc- 
curs in men and women employed in the sorting of rags in paper-factories, 
is in a part of the cases nothing more than an anthrax infection. The 
spores taken into the lungs in the respired air develop in the bronchi and 
alveoli, in the lymph-spaces of the lungs and pleura and in the bronchial 
glands, and i^enetrate also into the vessels. Their growth causes inflam- 
matorj^ processes in the lungs, as well as serous hsemorrhagic exudations 
into the pleural cavity and the mediastinal tissue, and swellings of the 
lymph-glands. It may also lead to the production of necrotic foci in the 
lungs, and in the bronchial and tracheal mucosa. 

Mice, rabbits, sheep, horses, and sparrows are very susceptible 
to anthrax; white rats, dogs, and Algerian sheep are less susceptible 
or immune. Cattle are easily infected through the taking in of the 
spores from the alimentary canal, but are less susceptible to inocu- 
lation. Formation of spores does not take place in the tissues and in 
the blood. 

A marked attenuation of anthrax-bacilli may be produced by keeping the bacilli for 
ten minutes at a temperature of 55° C. (Toussaint) or for fifteen minutes at 52° C, or 
for twenty minutes at 50° C. (Chauveau), or further through the influence of oxygen 
under liiiih pressure {Cliauveau). The bacilli attenuated by exposure for a short time 



688 



THE PATHOGENIC FISSION- FUNGI. 



to high temperatures quickly regain their virulence ; those attenuated at lower tem- 
peratures remain weakened for many generations. 

The addition of carbolic acid to the nutrient fluid in a proportion of 1 : 600 permits 
the further development of anthrax-bacilli, but destroys their virulence within twenty- 
nine days {Chamberland, Roux). Likewise, an attenuation may be produced by the 
addition of potassium bichromate (1 : 2,000-1 : 5,000). The addition of carbolic acid up 
to 1 : 800 hinders at the same time the formation of spores. 

Through cultivation of the bacilli at 42-43° C. {Toussaint, Pasteur, Koch), their 
virulence may be so weakened that they no longer kill first sheep, then rabbits and 
guinea-pigs, and finally mice. If the temperature is kept in the neighborhood of 43° C. 
this result may be obtained in six days; at 42° C. it may require about thirty days to 
decrease the virulence to this extent (Koch). By first inoculating with bacilli which 
kill mice but are harmless for guinea-pigs, and afterward inoculating with bacilli Avhich 
kill guinea-pigs but not strong rabbits, an immunity against anthrax may be obtained 
in sheep and cattle but not in the case of mice, guinea-pigs, and rabbits. Such protec- 
tive inoculations are, however, not of practical value, since, in order to protect against 
natural infection with spores from' the intestinal canal, such virulent inoculation-mate- 
rial must be used that a large per cent, of sheep (ten to fifteen per cent.) die from the 
inoculations. Further, the protection afforded by the inoculations is of very short 
duration, and the inoculation must be repeated within a year's time. 

According to observations by Eoux and Chamberland anthrax bacilli wiiich are 
cultivated in bouillon to which a small amount of potassium bichromate (1:2.000) or 
carbolic acid (1 to 2 : 1,000) has been added, permanently lose their power of spore -forma- 
tion while retaining their virulence. 

According to Koch, anthrax-bacilli may be cultivated in the presence of abundance 
of water upon potatoes and in an alkaline or neutral hay-infusion, cold infusions of pea- 
straw, on mashed barley and mashed wheat, in the juice of turnips, on maize, legumi- 
nous seeds, and numerous dead plants. Consequently they are able to grow and 
develop outside of the animal body — for example, in marshy regions and on river-banks 
(i?. Koch). The entrance into the animal body is to be regarded as an accidental excur- 
sion of ectogenic bacilli. According to Soyka the development of spores takes place 
very quickly in a moist medium containing the necessary nutrient material at tempera- 
tures above 15° C. According to Kitt the dung of cattle forms a nutrient substratum 
for the bacilli. 

Literature. 

(BaciUus Anthracis.) 

Behring: Beitrage zur Aetiologie des Milzbrandes. Zeitschr. f. Hyg., vi., vii., 1889. 
Bleuler: Hautmilzbrand. Correspbl. f. Schweizer Aerzte, 1884. 
Blumer: Anthrax Septicaemia. Bull, of Johns Hopkins Hosp., vi., 1895. 
Bourg-eois: Traite pract. de la pustule maligne, etc., Paris, 1861. 
Brauell: Unters. betreffend den Milzbrand. Virch. Arch., 11 Bd., 1857. 
Buisson: Charbon intestinal chez I'homme. Arch, de med. exp., i., 1889. 
Czaplewski: Unters. iib. d. Immunitat d. Tauben gegen Milzbrand. Zeit. f. Hvff., 

xii., 1893. ' 
Davaine: Compt. rend, de I'Acad. des sciences, 1863, 1864, 1865, 1868, 18T0, 1873. 

Republished in L'ceuvre de C. J. Davaine, Paris, 1889. 
Dittricb.: Prim. Milzbrandinfection des Magendarmkanales. Wien. klin. Woch.. 1891. 
Eppinger: Die Hadernkrankheit, Jena, 1894. 

Frank: Milzbrandimpfung. Zeitschr. f. Thiermed., vii., Suppl., 1884. 

Hoifa: Die Natur des Milzbrandgiftes, Wiesbaden, 1886; Zur Lehre d. Sepsis u. d. 

Milzbrandes. Langenbeck's Arch., 39 Bd., 1889. 
Jacobi: Vier Falle v. Milzbrand beim Menschen. Zeitschr. f. klin. Med., 17 Bd., 1890. 
Joline: Morphologic der Milzbrandbacillen. Deut. Zeitschr. f. Thiermed., xix., 1893. 
Karg: Verhalten der Milzbrandbacillen in der Pustula maligna. Fortschr. d. Med., 

vi., 1888. 

Klett: Sporenbildung d. Milzbrandb. bei Anam-obiose. Zeit. f. Hvg., 35 Bd., 1900. 
Koch, R.: Beitr. z. Biol. d. Pfl. v. F. Cohn, 2 Bd., p. 272. Mittheil. a. d. K. Gesund- 

heitsamte, Berlin, 1881, 1884; Ueber die Milzbrandimpfung, 1882. 
Koch, W.: Milzbrand und Rauschbrand. Deut. Chir., 9 Lief., 1886. 
Krumbholz: Darmmilzbrand. Beitr. v. Ziegler, xvi., 1894. 

Kurloff: Im Laboratorium acquirirte Milzbrandinfection. Deut. Arch. f. kl. Med., 
xliv., 1889. 

Lewin: Milzbrand beim Menschen. Cbl. f. Bakt., xvi., 1894. 
Lodge: La maladie des trieurs de laine. Arch, de med. exp., 1890 



BACILLUS TYPHI ABDOMINALIS. 



589 



Lubarsch: Milzbrand. Ergebn. d. allg. Path., v., 1900. 

Martinotti u. Barbacci: Ueb. d. Physiopathologie d. Milzbrandes. Fortschr. d. 
Med., ix., 1891. 

Melnikow: Kimstlicbe Immunitat d. Kaninchen geg. Milzbrand. Zeit. f. Hyg., 
XXV., 1897. 

Mliller: Der Milzbrand der Ratten. Fortschr. d. Med., 1893; Aeusserer Milzbrand 

des Menschen. Deut. med. Woch., 1894 (Lit.). 
Palm: Histologic des ausseren Milzbraudcarbunkels. Beitr. v. Ziegler, ii., 1888. 
Paltauf: Aetiologie d. Hadernkrankheit. Wien. klin. Woch., 1888. 
Parmier; La toxine charbonneuse. Ann. de I'lnst. Pasteur, 1895. 
Pasteur: La vaccination charbonneuse, Paris, 1883. 

Pawlowsky : Verhalten d. 31ilzbrandbacillen im Organismus. Virch. Arch., 108 Bd., 
1887. 

Physalix: Xouv. rech. sur la maladie charbonneuse. Arch, de med. exp., iii., 1891. 
Pianese: La capsula del B. anthracis. Giorn. dell' Assoc. di Nat., 1891. 
Pollender: Casper's Vierteljahrsschr. f. ger. u. off. Med., 8Bd., 1855. 
Reinbach: Zur Aetiologie d. Lungengangran. Cbl. f. ailg. Path., v., 1894. 
Rembold: Zur Aetiologie des 31ilzbrandes. Zeitschr. f. Hvg., iv., 1888. 
Roloff: Der Milzbrand, Berlin, 1883. 

Roux: Bacteridie charbonneuse asporogene. Ann. de I'lnst. Pasteur, iv., 1888. 
Straus: Cas de charbon mortel. Arch, de phys., i., 1883; Contrib. a I'anat. pathol. 

de la pustule maligne. Ann. de I'lnst. Pasteur, i., 1887. 
Toepper: Die neueren Erfahrungen lib. d. Aetiol. des Milzbrandes, Jena, 1883. 




Fig. m. Fig. 444. 

Fig. 443.— Typhoid-bacilli from a pure culture. Streak-preparation (metliylene-blue). X 1,000. 
Fig. 444.- Typhoid-bacilli with flagella. (After Bunge.) x 1,200. 

Toussaint: Rech. ex perimentales sur la maladie charbonneuse, Paris, 1889. 
Wag-ner: Le charbon des poules. Ann. de I'lnst. Pasteur, iv., 1890. 
Werigo: Developp. du charbon chez le lapiu. Ann. de I'lnst. Pasteur, 1894. 
Zorkendorfer : Darmmilzbrand. Prag. med. Woch., 1894. 

For literature concerning the intra-uterine transmission of the bacillus to the foetus, 
see § 150. 

§ 159. The Bacillus typhi abdominalis (Fig. 443), or the Bacterium 
typhi, is a fission-fungus which occurs chiefly in the form of plump rods 
2 to 3 fj- long, having rounded ends, and in cultures growing also in 
l^seudothreads. It is regarded as the cause of typhoid fever. When exam- 
ined alive in cultures it shows lively independent movements which are 
accomplished by means of flagella (Fig. 444) attached to the sides of the 
rods as well as to their ends. The flagella may be demonstrated by pro- 
per staining-methods. The bacillus was first observed in the intestinal 
lesions by Eberth and Koch, and described by them ; and was later iso- 
lated in pure cultures by Gaffky. A. Pf eiffer demonstrated its presence 
in the dejecta of typhoid patients, and his findings have been confirmed 
from many sides. According to Seitz, Hueppe, ]^eumann, and others 
it may also be present in the urine of typhoid patients. 

It stains well in cover-glass preparations, with gentian-violet, alka- 
line methylene-blue, and Bismarck brown. It is decolorized by Gram's 



590 



THE PATHOGENIC FISSION-FUNGI. 



method. It is difficiilt to demonstrate it in sections of hardened tissues, 
since the ceJl -nuclei also take the stain, and because the bacilli are not 
uniformly distributed but are usually found lying in the tissue in clumi)s. 

The bacillus may be cidtivated upon nutrient gelatin, agar-agar, and 
blood-serum, also in milk, and upon potato. Upon the last named it 
forms a coating which can be scarcely recognized by the naked eye ; but 
when the surface is touched with a platinum wire it becomes apparent 
that it is covered with a pellicle, which on microscopic examination is 
shown to consist of bacilli. 

On gelatin and agar-agar the bacilli form grayish-white, irregularly 
shax^ed, tlat growths. Gelatin is not iiqueiied. Milk in which the bacilli 
are grown is not changed externally. 

The cultures thrive at room-temperature as well as at body-temper- 
ature. Potato-cultures made in the usual manner, when kept between 
30° and 42° C, produce rods which have glistening bodies in their poles. 
Gatfky regarded these as si:)ores, and the majority of authors formerly 
acceiDted this view. According to Buchner and Pfuhl, however, these 
granules at the poles are degeneration phenomena, which occur particu- 
larly when acid is present in the culture medium. The polar granules 
represent condensed protoplasm, and therefore stain in fresh preparations 
more cpiickly with the aniline dyes than do the other parts of the ceil. 
The clear, colorless spots which are seen at the ends of the rods in dried 
and stained bacilli have been held to be identical with the polar granules 
and therefore regarded as spores; but are due, according to Buchner. 
to hollow spaces formed at the ends of the rods as the result of the 
retraction of the protoplasmic tube following the death and drying of 
the bacilli. Spore -formation has, therefore, not yet been demonstrated. 

In moist earth (Grancher, Deschamps), in pure and impure water, 
typhoid bacilli may remain alive for weeks. In artificial Seltzer water 
they do not die out for a longer period (Hochstetter). In privy v aults 
and fpecal masses, or in earth saturated with fsecal matter (Finkler. 
ITffelmann, Karlinski) they may under certain conditions live for weeks 
and months. 

Inoculations of the bacilli in the case of the animals ordinarily used 
for experiment do not produce a disease corresponding to typhoid fever 
in man. On the other hand, the experiments of Sirotinin, Beumer, Pei- 
per, and others have shown that the typhoid-bacilli produce active toxins 
and toxalbumins (Brieger ) which in large doses kill the animals, causing 
hyper?emia and swelling of the intestinal follicles, mesenteric glands, and 
the spleen. Ctiltures injected into the tissues cause a local inflammation 
of greater or less intensity. 

The bacilli or their spores gain entrance into the human organism 
through the drinking-water and food; though infection through the lungs 
is not to be excluded. According to the results of anatomical investiga- 
tions, they develop particularly in the intestinal wall, in the solitary and 
agminated foJJides of the small and large intestines, as well as in the mesen- 
teric lymph -glands and in the spleen. In the first-named place they cause 
an inflammatory infiltration of the mucosa and submucosa (Fig. 445, a^, bj 
whicii is extraordinarily rich in cells, and appears in the form of flat or 
somewhat rotmded elevations projecting above the inner surface of the 
intestines. An exudation of fibrin in the form of threads may take place 
both on the free stirface and in the deeper layers. Occasionally cellular 
inflammatory foci of limited extent also occur in the mtisctilaris (c, d^) 
and the serosa (ej. A part of the infiltrated tissue usually sloughs and 



BACILLUS TYPHI ABDOMINALIS. 



591 



is then cast ofi, so that ulcers are formed. lu other parts the infiltration 
may be absorbed and the swelling disappear. 

The swelling of the lymph-glands, which is likewise cansed by an ac- 
cumulation of cells and fluid, and occasionally of fibrin, ends either in 
healing through the absorption of the infiltrate or may also lead to a par- 
tial necrosis of tissue. In the spleen the pulp in particular swells, while 
its vessels are greatly dilated with blood, and the parenchyma later 
becomes crowded full of cells and fluid. 

According to recent investigations the bacilli are usually distribuied 
throughout other parts of the body, and it is probable that the inflammatory 
exudations in the lungs occurring at times during the course of typhoid 
fever are due in part to an increase of the bacilli within the lungs. It 
should always be borne in mind that aspiration-pneumonias are of very 
frequent occurrence in the lungs of typhoid patients, and also that sec- 




FiG. 445.— Typhoid fever. Section through the edge of a swollen Peyer's patch (alcohol, Bismarck, 
brown), a. Mucosa; b, subinucosa ; c, muscularis interna; d, museularis externa; c, serosa; «!, b], Ci, 
(i], C], different layers of the intestinal wall showing infiltration; /, sections of glands of Lieberkiihn ; y, 
follicle. X 15. • 

ondary infections (cocci) may take place from the ulcers and may give 
rise to metastatic inflammations in different tissues. The swellings of 
the mucosa and submucosa and of the perichondrial tissue, which often 
occur in the palate, throat, and larynx, are in part the result of the spe- 
cific infection, and in part of secondary disease. Moreover, typhoid 
bacilli have been demonstrated in the liver, gall -gladder, in the rose- 
spots of the skin, in the kidneys, central nervous system, testicles, in 
pleuritic and peritoneal fluids, in the periosteum, bone-marrow, etc., in 
part by means of the microscope and in part by means of cultivation. 
In all of these regions they ms>y cause degeneration and inflammation, 
and give rise to suppuration, so that the inflammations occurring during 
the course of typhoid fever owe their origin sometimes to the dissemina- 
tion and localization of the typhoid-bacilli, and sometimes to secondary 
or mixed infections. 

Neuhauss demonstrated the presence of typhoid -bacilli in the spleen 
of a four- months foetus, the mother aborting during an attack of typhoid 



592 



THE PATHOGENIC FISSION-FUNGI. 



fever. Eeher, Ebeith, Chant emesse, Widal, and Ernst have reported 
similar cases. 

Since the typhoid bacillns produces toxins and toxalbumins, the 
sympto]ns of the disease are for the greater part to be referred to the 
intoxication. In the course of typhoid fever there appear in the blood 
certain bactericidal substances which cause a degeneration of typhoid- 
bacilli (cf. § 31). This may be demonstrated by the fact that (Widal- 
Gruber reaction), through the addition of serum from an individual ill 
or convalescent from typhoid fever, to a bouillon-culture of freely motile 
typhoid-bacilli, the latter become motionless, clump together (agglutina- 
tion), sink to the bottom and die. This reaction may be used as a means 
of diagnosis, but is not of absolute certainty, since agglutination may be 
produced by the serum of individuals who have not had typhoid fever, 
and may be absent in the case of typhoid (Fischer). 

The cultures of typhoid-bacilli show but few characteristic properties, and are 
therefore distinguished with difficulty from other widely distributed bacteria. Their 
properties are very similar to those of the Bacillus coli communis (cf. ^ 160). As a dif- 
ferential point may be mentioned the fact that typhoid bacilli produce no indol, while 
other similar bacilli, including the colon bacillus produce indol, so that bouillon-cul- 
tures turn red on the addition of potassium nitrite and sulphuric acid. Further, the 
typhoid-bacillus produces no gas in a two-per-cent. glucose-bouillon while the colon- 
bacillus produces gas. Finally, the typhoid-bacillus produces a faint acidity in milk 
without coagulation, while the colon-bacillus causes a strong acidity and coagulation 
of the milk within from twenty -four to forty-eight hours at 37" C. 

Literature. 

{Bacillus of Typlioid Fever. ) 

Arustamoff: Zur Frage lib. d. Entstehung d. tvphosen Pneumonic. Cbl. f. Bakt., 

iv. . 1889. 

Babes: Ueber Variabilitat und Yarietateu des Typhusbacillus. Zeitschr. f, Hyg., ix., 
1890. 

Beumer: Aetiologie d. Typhus (Xachweis d. Bacillen im Trinkwasser). Deut. med. 
Woch., 1887. 

Beumer u. Peiper: Aetiolog. Bedeutung d. Tvphusbacilleu. Zeit. f. Hyg., i., 1886, 
il., 1887. 

Buchner: Ueber die vermeintl. Sporen der Typhusbacillen. Cbl. f. Bakt., iv,, 1888. 
Bunge: Zur Kenntniss der geisseltragenden Bakterien. Fortschr. d. Med., xii., 1894. 
Buschke: Lebeusdauer d. Tvphusbacilleu in ostitischen Herden. Fortschr. d. Med., 
xii.. 1894. 

Chantemesse et Widal: Bacille tvphique. Arch, de phys., ix., 1887; Ann. de I'lnst. 
Past.. 1892. 

Chiari: Cholecystitis typhosa. Prag. med. Woch., 1893.; Zeit. f. Heilk., xv., 1894. 
Coleman and Buxton: Paratyphoid Infections. Amer. Jour, of Med. Sc., 1902. 
Cyg-naus: Studieu liber den Typhusbacillus. Beitr. v. Ziegler, vii., 1890. 
Dmochowski u. Janowski: Eiterung erreg. Wirkung d. Typhusbacillus. Beitr. v. 

Ziegler, xvii., 1895 (Lit.). 
Ebermaier: Knochenerkrankungen bei Typhus. Deut. Arch. f. klin. Med., 44 Bd., 

1889. 

Eberth: Yirch. Arch., 81 Bd. ; Samml. klin. Vortr., No. 126; Geht der Typhusbacil- 
lus auf den Fotus liber? Fortschr. d. Med., vii., 1889. 

Faulhaber: Bakterien in d. Nieren bei acuten Infectionskrankheiten. Beit. v. Zieg- 
ler, X., 1891. 

Fischer: Werth der Widal'schen Reaction. Zeitschr. f. Hyg., 32 Bd., 1899. 
riexner: Certain Forms of Infection in Typhoid Fever. Johns Hopkins Hosp. Rep., 

v. , 1895; Unusual Forms of Infection with the Typhoid Bacillus, etc, Johns 
Hopkins Hosp. Rep., 1900. 

Forster: Baktericide Wirkung d. Blutserums v. Typhuskranken. Zeitschr. f. Hyg., 
xxiv., 1897 (Lit.). 

Frankel, E. : Complication v. Abdominaltyphus. Jahresber. d. Hamburg. Kran- 
kenanst., i., 1890; Roseola typhosa. Zeitschr. f. Hyg., 34 Bd., 1900. 



BACILLUS COLI COMMUNIS. 



593 



Frankel, E. u. Sirnimonds: Die iitiologiscbe Bedeutung d. Typhusbacillen, Leipzig, 
18SG. 

Gaffky: Aetiolo2;ie d. Abdominaltyplms. Mittheil. a. d. K. Gesimdheitsamte, Berlin, 
18«4. 

Gasser: Le bacille typliique. Arch, de med. exp., iii., 1891. 

Germano ii. Maurea: Typhusbac. ii. ahnliclie Bakterien. Beitr. v. Ziegler, xii., 1893. 
Grancher et Deschamps: Le bacille typhique dans le sol. Arch, denied, exp,, i., 
1889. 

Hamilton: The Fly as a Carder of Typhoid. Jour, of Amer. Med. Ass., 1903. 
Hesse: Unsere Nahrungsmittel als Nahrboden f. Typhus u. Cholera. Zeitschr. f. 
Hyg., v., 1889. 

Hiss: Studies in the Bacteriology of Typhoid Fever, etc. Med. News, 1901; New 

and Simple Media for the Differentiation of the Colonies of Typhoid, Colon, and 

Allied Bacilli. Jour, of Med. Res., 1902. 
Hodenpyl : On the Occurrence of Typhoid Fever without Characteristic Lesions of the 

Small Intestine. Stud, from Dept. of Path, of Columbia University, 1897-98. 
Holz: Exp. L^nters. lib. d. Nachweis d. Tj^phusbacillen. Zeitsch. f. Hyg., viii., 1890. 
Janowski: Zur Biologic d. Typhusbacillen. Cbl. f. Bakt., viii., 1890. 
Jatta: Agglutination d. Typhusbacillus u. d. Colibacillen. Zeitschr. f. Hyg., 33 Bd., 

1900 (Lit.). 

Johnston : Paratyphoid Fever. Amer. Jour, of Med. Sc. , 1902. 
Karlinski: Typhusbacillen in t^qDhosen Dejectionen. Cbl. f. Bakt., vi., 1889. 
Kitasato: Verh. d. Typhusbacillus zu saure- u. alkalihaltigen Nahrboden. Zeitschr. 
f. Hyg., iii., 1888. 

Klebs: Bacillen im Typhusdarm. Arch. f. exp. Path., xii., xiii., xv., 1880-82. 
Mallory: Histological Study of Typhoid Fever. Jour, of Exp. Med., 1898. 
Meisels: Ueber das Vorkommen von Typhusbacillen im Blute. Wien. med. Woch., 
1886. 

Muscatello: Sul potere piogeno del bacillo di Eberth. La Riforma med., 1890. 
Neuhauss: Nachweis d. Typhusbacillen am Lebenden (in Roseolaflecken). Berl. kl. 
Woch., 1886. 

Neumann: Ueber Typhusbacillen im Urin. Berl. klin. Woch., 1890. 
Orloff: Aetiologie der d. Typhus abdom. complicirt. Eiterungen. Cbl. f. Bakt., viii., 
1890. 

Osier, Flexner, Blumer, Reed and Parsons : Studies in Typhoid Fever. J. Hop. 
Hosp. Rep., v., 1895. 

Petrusch-ki: xiusscheidung d. Typhusbacillen durchUrin. Cbl. f. Bakt., xxiii., 1898. 
Pfeiffer: Nachweis d. Typhusbacillen im Darminhalt u. Stuhlgang. Deut. med. 
Woch., 1885. 

Pfeiffer u. KoIIe: Spec. Immunitatsreaction d. Typhusbacillen. Zeitschr. f. Hyg., 
xxi., 1896. 

Q,uincke: Zur Pathologic des Abdominaltyplms. Berl. klin. Woch., 1894. 
Remy et Sugg: Rech. sur le bacille d'Eberth-Gaffky, Gand, 1893. 
Rodet: Aggjutin. du bac. d'Eberth et du B. coli. Jour, de phys., ii., 1900. 
Sanarelli: Et. sur la lievre typhoide experimentale. Ann. de I'lnst. Pasteur, vi., 
1892. 

Seitz: Bericht iib. die Aetiologie d. Abdominaltyphus. Cbl. f. Bakt., ii., 1887. 
Sirotinin: Die Uebertraguner v. Typhusbacillen auf Versuchsthiere. Zeitschr. f. 
Hyg., i., 1886. 

Thayer : Observations on the Blood in Typhoid Fever. Johns Hopkins Hospital Re- 
port, 1901. 

Tictine : Meningitis et abces produits par le bacille de la fievre typh. Arch, de med. 
exp., 1894. 

TJffelmann: Lebensfahigkeit d. Typhus- u. Cholerabacillen in Facalmassen. Cbl. f. 
Bakt., v.. 1889. 

Widal et Sicard: Le serodiagnostic. Ann. de I'lnst. Pasteur, 1897 (Lit.). 
Winterberg: Typhus-Agglutinin. Zeitschr. f. Hyg., 32 Bd., 1899. 

§ 160. The Bacillus coli communis or the Bacterium coli commune 
(Escherich) is a fission -fungus which is constantly present in the intes- 
tinal tract of man as well as of the mammalia. The bacilli are rods 
2-3 long and 0.3-0.4 p. thick. They are motile and may possess as 
many as twenty flagella on one rod (Bunge, Luksch, Giinther). The 
bacilli grow at room -temperature as well as at the temperature of the 
incubator. They form within the gelatin small, round, white colonies; 
upon its surface pellicle -like coatings. Upon potatoes they form moist 



594 



THE PATHOGENIC FISSION- FUNGI. 



coatings of the yellow color of maize or i^ease (Giintlier). They do not 
form spores; and are not stained by Gram's method. 

The Bacillus coU is very similar to the typhoid bacillus, but may be 
differentiated from it by proi)er methods of cultivation and by the em- 
ployment of suitable reactions (cf. § 159). It was formerly regarded as 
a harmless saprophyte of the colon ; but from later investigations it can- 
not be doubted that it also possesses pathogenic properties and may cause 
degenerations and inflammations in various tissues. Under suitable condi- 
tions (j)erf oration or incarceration of the intestine, or impaction of f?eces) 
it may pass into the i^eritoneal cavity and excite purulent inflammations, 
or at least take part with other bacteria in the production of inflamma- 
tion. Further, it not infrequently gains access to the bile -passages and 
gall-bladder, as well as to the descending urinary passages and the kid- 
nej'S, giving rise to inflammations of varying intensity. The bacillus 
has also been found in the meningeal exudate in certain cases of sepsis ; 
it has been demonstrated also in pericarditis, bronchopneumonia, stru- 
mitis, angina of scarlet-fever, acute yellow atrophy of the liver (Stroebe, 
von Kahlden), and it cannot be doubted that it may be the cause of the 
affections named. 

The similarity between the colon-bacillus and the typhoid-bacillus has led various 
authors to assume that the two bacilli are only varieties of the same species, and that 
the two forms may pass over into each other. At the present time the view prevails 
that the two bacilli are to be wholl}' separated from each other 159.) Moreover, the 
form of bacillus which is described as colon-bacillus is not a very distinct form, but rep- 
resents rather a group of different varieties. Three to four days after the inoculation of 
an animal with colon-bacilli the blood-serum of the infected animal produces an agglu- 
tination of colon-bacilli (Jatta), which is most marked in the case of that variety Avhich 
was used for the inoculation. Colon-bacillus serum {Jatta) agglutinates typhoid-bacilli 
more markedly than does normal blood-serum. On the other hand, typhoid serum can 
agglutinate different varieties of colon-bacilli. 

Literature. 

(Bacillus CoU Communis.) 

Ackermann : Les. osteomyelitiques exper. prov. par bac. coli comm. Arch, de med. 
exp., vii., 1895. 

Adami, Abbott and Nicholson : On the Diplococcoid Form of the Colon Bacillus. 

Jour, of Exp. Med., 1899. 
Allen: Paracolon Infection. xVmer. Jour, of Med. Sc., 1903. 
Arloing: Rapport du bac. coli comm. avec le bac. d'Eberth. Lyon med., 1891. 
Arnaud: Eech. sur I'etiologie de la dysenterie. Ann. de ITnst. Pasteur, viii.. 1894. 
Bunge: Eur Kenntniss der geisseltragenden Bakterien. Fortschr. d. Med., xii., 1894. 
Buxton : A Comparative Studv of the Bacilli Intermediate between B. Coli Communis 

and B. Typhosus. Jour, of Med. Res., 1902. 
Gushing: A Comparative Study of Some Members- of a Pathological Group of Bacilli 

of the Hog Cholera Tvpe, Intermediate between the Typhoid and Colon Groups. 

Johns Hopkins Hosp. Bull., 1900. 
Dunbar: Unters. lib. Typhusbac. u. Bact. coli. Zeitschr. f. Hyg., xii., 1892. 
Ford: Varieties of Colon Bacilli Isolated from Man. Mont. Med. Jour., 1900. 
Hofmeister: Zur Charakteristik d. Eklampsiebacillus Gerdes. Fortschr. d. 3Ied., x., 

1892. 

Janowski: Die Ursachen der Eitorung. Beitr. v. Ziegler, xv., 1894. 
Jatta: Agglutination d. Typhusb. u. d. Organism, d. Coligruppe. Zeitschr. f. Hyg., 
32 Bd., 1900 (Lit.). 

V. Kahlden: Ueb. acute gelb. Leberatrophie u. Lebercirrhose. Munch, med. Woch., 
1897. 

Kamen: Aetiologie der Winckel'schen Krankheit (Bac. coli). Beitr. v. Ziegler, xiv., 
1893. 

Kiessling: Das Bacterium coli commune. Hyg. Rundschau, 1898. 
de Klecki: Pathogenie de I'appendicite. Ann. de ITnst. Pasteur, 1899. 
Lartig-au: The Bacillus Coli Communis in Human Infections (Lit.). Studies from the 
Dept. of Path, of Columbia University, 1901-02. 



BACILLUS PNEUMONIAE. 



595 





Lesage et Macaigne: Virulence du bact. coli. Arch, de med. exp., iv., 1892. 
Libman: Paracolon Infection. Jour, of Med. Res., 1902. 
Longcope: Paracolon Infection. Amer. Jour, of Med. Sc., 1902. 
Neisser: Uuters. lib. d. Typhusbac. u. Bact. coli. Zeitschr. f. klin. Med., xv., 1893, 
Oker-Blom: Eindringen des B. coli in die Darmwand. Cbl. f. Bakt., xv., 1894. 
Pisenti: Sui rapporti del B. coli coUa infezione tifosa. Arch. p. le Sc. Med., xviii., 
1894. 

Renault: Du bact. coli comm. dans I'infection urinaire, Paris, 1893. 
Rodet et Roux: Bac. d'Eberth et B. coli. Arch, de med. exp., iv., 1892. 
Roger: Toxicite des prod, solubles du bact. coli. Arch, de phys., 1893. 
Schmidt u. Aschoff: Die Pyelonephritis in anat. u. path. Be- 

ziehung u. die ursachl. Bedeutung d. Bact. coli comm. f. d. 

Erkrankung der Harnwege, Jena, 1893. 
Stern: Pathogene Wirkung des Colibacillus. Deut. med. Woch., 

1893. 

Stroebe: Acute Leberatrophie. Beitr. v. Ziegler, xxi., 1897 (Lit.). 
Trambusti: ZurFrage d. Identitat d. Bact.Eberth u. d. Bact. coli. 

Cbl. f. ailg. Path., iii., 1892. 
Wurtz : Le bacterium coli commune. Arch, de med. exp. , v. , 1893. 

^ 161. The Bacillus pneumoniae or the Bacterium 
pneumoniw is a bacillus discovered by Friedlander and 
Frobenins ; and by them assumed to be the cause of in- 
flammations, particularly of the lungs, nose (oz^ena) 
middle ear, and meninges, more 
rarely of other organs. It is re- 
garded by Friedlander as the chief 
cause of croupous pneumonia, but 
this view is without doubt incor- 
rect (cf. § 153). According to 
Weichselbaum it ' can be demon- 
strated in only about five per 
cent, of the cases of lobar pneu- 
monia. Baumgarten and others 
hold that its pathogenic signifi- 
cance is not yet firmly established, 
inasmuch as other bacteria are found in association 
with it when present in the lungs. 

The bacilli are found in the alveolar exudate, as 
well as in the pleuritic exudates that occur at the same |f i 
time with the pulmonary inflammation. They appear 
partly in the form of rods (Fig. 446, h), partly as oval 
cells (a), Sbiid not infrequently form short chains. Since 
the oval cells are more numerous than the rod forms, 
the bacillus was originally classed with the cocci. 

The bacilli possess a hyaline, mucin-like capsule, 
soluble in alkalies, and insoluble in acetic acid, which 
forms a common sheath around the chains of the bacilli 
(Fig. 446). Independent motion has not been observed. 

When treated with iodine and alcohol after staining with gentian- 
violet the bacillus loses its stain and is in this way distinguished from 
the diplococcus. For staining it in sections with demonstration of the 
capsule Friedlander recommends the employment of an acid gentian-vio- 
let solution (concentrated alcoholic gentian-violet solution 50 parts, dis- 
tilled water 100 parts, acetic acid 10 parts). After staining in this for 
twenty-four hours the sections are washed for a short time in a 0.1 -per- 
cent, solution of acetic acid. 

The bacilli grow upon nutrient gelatin at room -temperatures, and 



Fig. 446.— Bacillus pneu- 
monise (Friedlander). a. 
Oval cells and rows of cells 
with gelatinous capsule ; Z), 
rod with gelatinous capsule. 
X 800. 



1 *' 'i 



FiCx. 447.— Nail-shaped 
stab-culture of the 
Friedlander pneumonia- 
bacillus in gelatin. 



596 



THE PATHOGENIC FISSION-FUNGI. 



form upon the surface of the gelatin iDorcelain- white, button -shaped cul- 
tures consisting of oval and rod-shaped cells jDossessing no capsules. 
Stab-cultures in gelatin are nail-shaped (Fig. 447), the growth forming 
a knob-like prominence at the entrance of the stab-canal. This charac- 
teristic the pneumonia-bacilli share in common with many other bacteria. 
On blood-serum they form translucent, gray colonies; upon agar-agar 
jelly-like, grayish-Avhite, and upon potatoes grayish- white or j'ello wish- 
white, creamy colonies. Spore-formation has not been observed. 

Eabbits are almost completely immune to inoculation of the lungs. 
Mice on the other hand die of pleuritis and disseminated pneumonia 
within eighteen to thirty hours after injection of the bacilli into the 
lungs ; the exudate as well as the blood contains bacilli with gelatinous 
capsules, partly free and partly enclosed within ce'lls. A tyi)ical lobar 
pneuanonia cannot be i^roduced in the ordinary experimental animals by 
inoculation. 

According to Fricke the bacterium of Friedldnder is the chief representative of a 
group of bacteria Avliich are classed together under tlie name Bacillus miicosus capsu- 
latus, and represent varieties of a single species. The fission-fungus described as the 
ozsena-bacillus is identical with the pneumonia-bacillus, probably also the bacillus from 
the milk-faeces of nurslings described as the Bacterium lactis aerogenes (Escherich). It 
is possible that a greater etiological significance may be attached to it in so far as the 
origin of many diarrhoeas is concerned. 

Literature. 

(Bacillus Fneumonice.) 

Emmerich: Pneumoniekokken in der Zwischendeckfiillung. Fortschr, d. Med., ii., 
1884. 

Frankel: Pneumoniekokken. Zeitschr. f. klin. Med., x., xi. ; Deut. med. "Woch., 
1886. 

Fricke: Ueb. d. sog. Bacillus mucosus capsulatus. Zeit. f. Hyg., xxiii., 1896 (Lit.). 
Friedlander: Pneumoniekokken. Yirch. Arch., 87 Bd., 1882; Fortschr. d Med., 1., 
1883. 

Grrimbert: Pneumobacille de Friedlander. Ann. de ITnst. Pasteur, 1896. 
Weichselbaum : L. c, § 153; Von einer Otitis media suppurativa ausgehende, durch 

den Bacillus pneumoniae bedingte Allgemeininfection. Monatsschr. f. Ohrenheilk,, 

1888. 

Wilde: Ueber d. Bacillus Friedlander. Cbl. f. Bakt., xx., 1896. 

§ 162. As the influenza=bacillus (Fig. 448) there was described by 
E. Pfeifier, in the year 1892, a bacillus whose occurrence in influenza 
has been many times confirmed ; it is now regarded as the cause of infl.u- 
enza. In individuals suffering from influenza it is found in th« catarrh- 
ally affected respiratory passages, occasionally also in the lungs ; and the 
small bronchi may contain enormous numbers of the bacilli in pure cul- 
ture. It is assumed that their multiplication in the respiratory tract 
gives rise to the inflammation, and that the bacilli produce poisons, 
which, when absorbed, cause the symptoms characteristic of influenza. 
The bacilli may also pass into the blood and become spread throughout 
the body. The inflammatory changes of internal organs occurring during 
influenza are to be referred in i^art to the influenza-bacillus, in part to 
the poisons produced by them, and in part to secondary infections. 

The influenza-bacilli are very small, thin rods with rounded ends 
(Fig. 448), which lie separate or joined together in twos. They stain 
with the ordinary aniline dyes, but not by Gram's method. They may 
be cultivated at the body-temperature upon blood-agar or upon agar that 



BACILLUS DIPHTHERIA. 



597 




has been smeared with human or pigeon blood. They form npon this 
medium small, drop -like colonics as clear as water. They cannot be 
cultivated upon the other usual media. Spore - 
formation has not been observed. In apes a 
catarrhal inflammation of the respiratory tract 
may be produced by intratracheal injections 
of pure cultures. Babbits may be poisoned 
through the incorporation into their bodies of 
cultures ; and are alf ected in consequence by a 
paralytic weakening of the muscles and dysp- 
noea. According to Cantani the poison pro- 
duced by the bacilli exerts its effects partic- 
ularly upon the central nervous system. 

According to investigations by GzapleicsM and Rensel (" Bakteriolog. Untersuch. liber 
Keuclihusten, " Centrhl.f. Bakt., xxii., 1897) SimX KopUk ("Die Bakteriologie des Keucli- 
hustens," Centralhl. f. Bakt., xxii., 1897), there is found in the respiratory tract in 
whoopmg=cough a small, non-motile bacillus similar to the influenza-bacillus, which is 
thought to be the cause of whooping-cough. Luzzatto (" Zur Aetiol. des Keuchhustens, " 
Centralhl. f. Bakt., xxvii., 1900) found in cases of whooping-cough two bacilli, but was 
unable to determine with certainty their pathogenic significance. Joclimann and Krause 
("Aetiol. des Keuchhustens," Zeit. f. Hyg., 36 Bd., 1901) found in whooping-cough a 
bacillus resembling the influenza-bacillus {Bacillus pertussis, Eppendorf) ; this could be 
cultivated upon media containing hcemoglobin ; they regard it as the cause of whooping- 
cough. Their bacillus is not identical with the one described by Czapleicski/ and Hensel. 



Fig. 448. — Influenza-bacilli 
and pus-corpuscles, from spu- 
tum (fuchsin). X 1,000. 



Literature. 



(Bacillus of Influenza. ) 

Baumler: Die Influenzaepidemie, 1893-94, in Freiburg i. Br. Miinch. med. Woch., 
1894. 

Beck: Influenza. Ergebn. d. allg. Path., v., 1900 (Lit.). 

Canon: Mikroorganismen im Blute von Influenzakranken. Virch. Arch., 131 Bd., 
1893. 

Cantani: Wirkung d. Influenzabacillen a. d. Centralnervensyst. Zeitsch. f. Hyg., 
xxiii., 1896 (Lit.). 

Grasburger. Zur Bakteriologie d. Influenza. Zeitsch. f. Hyg., xxv., 1897. 

Huber: Leber den Influenzabacillus. Zeitschr. f. Hyg., xv., 1893. 

Kitasato: Leber den Influenzabacillus. Deut. med. Woch., 1892. 

Kruse: Aetiologie der Influenza. Deut. med. Woch., 1894. 

Kuskow: Pathol. Anatomic d. Grippe. Virch. Arch., 139 Bd., 1895 (Lit.). 

Nauwerck: Influenza u. Encephalitis. Deut. med. Woch., 1895. 

Ophlils : Infection of the Rectum with Secondary Infection of the Liver, Caused by 

the Bacillus Influenzae Similis. Amer. Jour, of Med. Sc., 1901. 
Pfeiffer, A.: Die Aetiologie der Influenza. Zeitschr, f. Hyg., xiii., 1893. 
Pfuhl u. "Walter: Influenzabacillen im Centralnervensystem. Deut. med. Woch., 

1896. 

Weicliselbaum : Aetiologie u. path. Anat. d. Influenza. Wien. klin. Woch., 1892. 

§ 163. The Bacillus diphtherise (Fig. 449) was first thoroughly studied 
by Loffler ; it is found in the croupous membrane occurring in diph- 
theria, and is regarded as the cause of this disease. In the internal 
organs, as the spleen and lymph-glands, it is either entirely absent or 
present in such slight numbers that it can be demonstrated only by 
methods of cultivation. 

The bacilli are 1.5-3 /j. long, often somewhat thickened (club-shaped) 
or pointed at the ends. When stained the bacilli appear spotted or 
granular. They stain best in a staiuiug-solution composed of 30 c.c. of 
concentrated alcoholic methylene -blue solution in 100 c.c. of 0.0001 per 
cent, potassium hydroxide solution, after which the sections are treated 



598 



THE PARASITIC FISSION- FUNGI. 



for a few seconds in a 0.5-per-cent. solution of acetic acid and then with 
alcohol. In stained sections the bacilli often appear segmented. They 
also stain by Gram's method, provided the treatment with Lugol's solu- 
tion and alcohol is of brief duration. 

Diphtheria- bacilli grow best in the presence of air (Loffler) on a mix- 
ture of three parts of calf's or sheep's serum, and one part of neutralized 
veal -bouillon, to which one per cent, of peptone, one per cent, of grape- 
sugar, and 0.5 per cent, of common salt are added; or upon blood-serum 
and agar-agar with an addition of ten per cent, glycerin or of sugar-con- 
taining bouillon (Kolisko, Paltauf, Kitasato). 
*\ ^ They form grayish-white colonies. For their de- 

^ ^ velopment they need a temperature above 20° C. ; 

fiU\^<r'* ^^^y grow best at 33°-37° C. They are resistant 
/\'^'^- ^ to drying; but may be quickly killed by moist 

* ' # heat. Spore-formation has not been observed. 
^ ^ \ Guinea-pigs inoculated suhcutaneously with cul- 

^ ^ tures of diphtheria- bacilli die in two to three days 

^ fi#\ 'Vif (Loftier, Eoux, Yersin) ; whitish deposits and a 
n ^ "^^^ hsemorrhagic oedema are found at the point of the 

FIG. 449.-Dipiitheria-ba- inoculatiou. The inoculatiou-arca contains bacilli, 
si^LkTepJraC'n internal organs, on the contrary, are free. The 

lene-biue). X 1,000. introduction of cultures into the opened trachea of 

rabbits, chickens, and pigeons, as well as the inoc- 
nlation of the conjunctiva of rabbits and the vagina of guinea-pigs is followed 
by an inflammation with the formation of a pseudomembrane. Sheep, 
horses, cats, dogs, cows, rabbits, and pigeons are susceptible to subcu- 
taneous inoculation. Eats and white mice are nearly immune. 

Eoux, Yersin, Loffler, Spronck, and others observed the later appear- 
ance of paralysis in pigeons and guinea-pigs surviving the inoculation. 
Eoux and Yersin assert that the intravenous injection of filtered bouillon- 
cultures free from bacteria will cause in guinea-pigs and rabbits after two 
to three days a severe illness characterized by paralysis and fatal termi- 
nation. 

The virulence of the cultures varies greatly. Di]3htheria bacilli pro- 
duce in the human body and also in cultures toxins, which may be pre- 
cipitated by alcohol and obtained as a whitish powder. This substance 
has been classed with the toxalbumins, but according to Brieger and Boer 
it is not an albuminous body. It is also formed when the bacilli are cul- 
tivated in alkaline urine (Guinochet). According to Kossel the poison 
is formed within the bacterial cell from its food-material and then se- 
creted. 

Water-solutions of the poison injected subcutaneously into animals 
cause local tissue -necrosis, ha)morrhagic oedema, and inflammation ; when 
taken up into the body-juices they give rise to pleural effusions, nephri- 
tis, fatty degeneration of the liver, and paralysis. 

Diphtheria in man is characterized by an inflammation involving usu- 
ally the mucous membrane of the pharynx, palate, arch of the palate, 
and upper respiratory passages. It appears as a febrile infectious dis- 
ease associated tvith symptoms of intoxication and gives rise to local croupous 
exudations, in part also to diphtheritic sloughings (cf. § 92, Figs. 189, 
190). The croupous membranes constitute the most striking feature of 
the disease ; they are found in the throat and nose usually in the form of 
circumscribed flat patches, more rarely uniformly spread over larger 
areas ; or, on the other hand, they may form a continuous layer lining 



BACILLUS DIPHTHERIA. 



599 



the larynx and trachea, or even the bronchi. Beneath the croupous 
membrane the epithelium is for the greater part lost ; and the connective 
tissue of the mucosa is hypergemic, infiltrated, and swollen (Fig. 190). 
In severe cases the superficial layers of the connective tissue are necrotic 
in places, most frequently in the tonsils, which are more or less, often 
markedly, swollen. Of the deeper tissues the neighboring cervical 
lymph-glands in particular are swollen, and often show, when examined 
microscopically, small foci of necrosis and degeneration. Of the inter- 
nal organs the kidneys especially are accustomed to show changes, in the 
form of a more or less severe fatty degeneration of the epithelium and 
of the cells of the capillary walls ; not infrequently they also present 
swellings and focal areas of small -celled infiltration. In the spleen 
there are frequently found areas of degeneration in the white -appearing 
follicles, in which the cells are more or less necrosed, in part disinte- 
grated and have lost their nuclei. In the blood many of the leucocytes 
show fatty degeneration. Degenerative changes and areas of inflamma- 
tion are not infrequently found in the heart-muscle. Paralyses are 
caused by degeneration and necrosis (Katz) of the ganglion- cells of the 
medulla oblongata and of the spinal cord and of the corresponding 
nerves. 

The lungs are not demonstrably changed by the diphtheria poison, 
but brouchopneamonia, due to the aspiration of irritating bronchial 
contents or to an extension of the bronchial inflammation to the respi- 
ratory parenchyma, is of frec[uent occurrence. 

The local infiammations of the mucous membranes as well as the symp- 
toms of intoxication may he caused by the diphtheria bacilli and their toxins 
(done ; but it must be noted that streptococci are almost regularly i^res- 
ent in the diseased area, and that a pure streptococcus infection may 
present the clinical and anatomical picture of a diphtheria When 
both bacteria are present the injurions effect of one may be supple- 
mented by that of the other, and the presence of streptococci appears to 
increase the virulence of the bacilli. In severe forms of dii)htheria 
streptococci are usually present in great numbers ; yet every streptococ- 
cus infection does not warrant a bad prognosis, since the virulence of the 
cocci varies greatly. 

In the course of the infection with diphtheria bacilli there arise in the 
body antitoxins, which nullify the poisonous action of the toxins, and aid 
and make possible recovery from the disease. The formation of anti- 
toxins follows the inoculation of animals with attenuated bacilli, and 
upon this rests the possibility of obtaining from animals (sheep, horses), 
that have been repeatedly inoculated with bacilli of increasing virulence, 
a serum which contains an antitoxin of value for therapeutic purposes 
(cf. § 32). 

Lehmann and JSenmann call the diphtheria bacillus corynehacterium on account of 
the club-shaped appearance of the rods. Since the bacilli can also form branching 
threads in cultures, they class it with the hyphomycetes, among which the tubercle-bacil- 
lus and the fungus of actinomyces (oospora) are also classed by them and others. 

Ehrlich {''t)\e Constitution des Diphtherie-Giftes," Deut. med. WocJienschr., 1898, 
p. 59T) distinguishes different kinds of poisons produced by the diphtheria-bacillus, 
namely, toxins and toxons, these again representing no bodies of definite unity, but 
breaking up into several subdivisions (prototoxin, deuterotoxin, and tritotoxin) which 
are distinguished by the different degrees of avidity with which they unite with the 
antitoxin. He further assumes that there are present in the poison-molecule tAvo atom- 
complexes independent of each other, one of which is of haptophorous nature and 
brings about the union with the antitoxin or with the corresponding side-chains of the 



600 



THE PATHOGENIC FISSION-FUNGI. 



cells. The other atom-complex is toxophorous— that is, it is the cause of the specific 
action of the poison (cf. § 32). 

According to Ldffler, von Hoffmann, Roux, Yersin, Bales, and others there are very 
frequently present in the mouth and throat bacilli, which are often designated pseudo= 
diphtheria bacilli. These resemble the true bacilli of diphtheria and can be distin- 
guished from them only in cultures. Since the diphtheria-bacilli can lose their viru- 
lence, it is not impossible {Ronx, Tersin) that both bacilli represent varieties of the 
same species. According to Kober and others diphtheria-bacilli are also found in the 
mouths of healthy individuals. 

Literature. 

(Bacillus JDiphtherice and Diphtheria. ) 

Babes: Les bacteries de la diphtheric. Ann. de I'lnst. de path, de Boucarest, ii., 1891; 

Virch. Arch., 119 Bd., 1890. 
Baginsky: Diphtheric u. diphther. Croup, Wien, 1898. 

Barbacci: Alterat. d. Milz, Lymphdriisen u. Leber bei Diplith. Cbl. f. allg. Path., 
vii., 1896. 

Barbier: De quelques associat. microbiennes dans la diphtheric. Arch, de med. exp., 

iii. , 1891. 

Behring": Die Geschichte d. Diphtheric mit Berticksichtigung d. Immunitatslehre, 
Leipzig, 1893. 

Bernheim: Mischinfection bei Diphtheric. Zeitschr. f. Hyg., xviii., 1894; Path- 

ogenese d. schweren Diphtheric, Wien, 1898. 
Blasi: Association bacter. dans la diphtheric. Ann. de I'lnst. Past., 1896. 
Bock: Bakt. Unters. liber die Aetiologie der Diphtheric. Zeitschr. f. Hyg., viii., 1890. 
Brieg-er u. Boer: Toxine d. Diphtheric. Deut. med. Woch., 1896. 
Chaillon et Martin: Et. clin. et bacter. sur la diphtheric. Ann. de I'lnst. Pasteur, 

1894. 

Colbet: Pseudodiphtheria Bacillus. Journ. of Path., iv., 1896. 

Councilman, Mallory and Pearce : A Study of the Bacteriology and Pathology of 
Two Hundred and Twenty -five Fatal Cases of Diphtheria. Jour, of Bost, Soc. of 
Med. Sc., 1900. 

Crocq: Alter, du syst. nerveux dans les paralys. diphth. Arch, de med. exp., 1895 
(Lit.). 

Denny : Morphology of B. Diphtherige, B. Pseudo-diphtherise, and B. Xerosis. Jour. 

of Med. Res., 1903. 
V. Dungern: Mischinfection bei Diphtheric. Beitr. v. Ziegler, xxi., 1897. 
Ehrlich u. Wassermann: Die Gewinnung d. Diphtherieantitoxinc. Zeitschr. f. 

Hyg., xviii., 1894. 
Escherich : Aetiologie u. Pathogenese der Diphtheric, Wien, 1894. 
Fliigg-e: Verbreitungsweise der Diphtheric. Zeitschr. f. Hyg., xvii., 1894. 
Frankel, C: Aetiolog. Bedeutung der Loflfler'schen Bacillen. Deut. med. Woch., 

1895. 

Froscb.: Verbreitung des Diplitheriebac. im Korper. Zeitschr. f. Hyg., xiii., 1893. 
Gorh.ani: Morphological Varieties of Bacillus Diphtheri£e. Jour, of Med. Res., 1901. 
Guinochet: Contr. al'et. de la toxine du bacille de la diphtheric. Arch, de med. exp., 

iv. , 1892. 

Henke: Exp. Erzeugung d. Diphtheric. Arb. a. d. path. Inst, zu Tubingen, ii., 1899. 
Hilbert: Mischinfection bei Diphtheric. Deut. Arch. f. klin. Med., 59 Bd., 1897; 

Steigerung d. Giftproduction an Diphtheriebacillcn durch Symbiose m. Strcpto- 

kokken. Zeitschr. f. Hyg., 29 Bd., 1898. 
Hill: Branching in Bacteria with Special Reference to Bacillus Diphtherise. Jour, of 

Med. Res., 1902. 
Katz : Diphthcrische Lahmungen. Arch, f . Kinderheilk. , 1897. 
Klein: Beitrage zur Aetiologie der Diphtherie. Cbl. f. Bakt., vii., 1890. 
Kober: Diphtheriebacillcn auf d. Mundschleimhaut gesunder Menschen. Zeitsch. f. 

Hyg., 31 Bd., 1899. 

Kondrevetzky : Rech. exp. s. I'immunisation centre la diphtherie. Arch, de med. 
exp., v., 1893. 

Kossel: Zur Kenntniss d. Diphtheriegiftes. Cbl. f. Bakt., xix., 1896. 

Kutscher: Nachweis d. Diplitheriebac. in d. Lunge. Zeitschr. f. Hyg., xviii., 1894. 

Loflaer: Entstehung der Diphtherie. Deut. med. Woch., 1890; Bedeutung der Mikro- 

organismen fur die Entstehung der Diphtherie. Mittheil. a. d. Kais. Gesundheit- 

samte, ii., Berlin, 1884. 
Madsen: Zur Biologic d. Diphtheriebacillcn. Zeitschr. f. Hyg., xxvi., 1897. 



BACILLUS TETANI. 



f)01 



Millard et Regaud: Myocardite diplitherique. Ann. de I'lnst. Pasteur, 1897 (Lit.)- 
Mouravieff: lufl. de la toxine diphtli. sur le syst. nerveux. Arcli de nied. exp., 1897. 
Oertel: Die Patliogenese der epidem. Diplitherie, Leipzig, 1887; Das diphtherische 

Gift. Deut. med. Wocli., 1890. 
Orth: Zur Geschiclite der Diplitlierie. Arb. a. d. path. Inst, zu Gottingen, Berlin, 

1893. 

Peters: Diphtherial!. Pseudodiphtheria Bacilli. Journ. of Path., iv., 1896. 
Proschaska: Pseudodiphtheriabacillen d. Rachens. Zeitschr. f. Hyg., xxiv., 1897. 
Prudden: Studies on the Etiology of Diphtheria. Med. Rec, JSTewl'ork, 1891. 
Roux et Martin: Serotherapie de la diphtheric. Ann. de I'lnst. Pasteur, viii., 1894. 
Roux et Yersin: Diplitherie. Ann. de i'lnst. Past., ii., 1888; iv., 1890. 
Schottelius : Wachsthum d. Diplitheriebac. in d. Milch. Cbl. f. Bakt., xx., 1896. 
Schlesinger: Diphtheric d. Conjunctiva. Miinch. med. Woch., 1901. 
Slawyk u. Manicatide: Variabilitat d. Diphtheriebacillen. Zeitschr. f. Hyg., 29 
Bd., 1898. 

Spronck: Pathogene Bedeutung d. Diphtheriebacillus. Cbl. f. allg. Path., i., 1890; 

Invasion des Diphtheriebacillus in d. Unterhaut d. Menschen. lb., iii., 1892. 
Wassermann u. Proskauer: Vom Diplitheriebac. erzeugte Toxalbumine. Deut. 

med. Woch., 1891. 

Welch: The Histological Changes in Exp. Diphtheria. Bull, of the Johns Hopk. 
Hosp., ii., 1891. 

Welch and Abbot: The Etiology of Diphtheria. Bull, of the Johns Hopk. Hosp., ii., 
1891. 

Williams : Persistence of Varieties of B. Diphtheria? and of Diphtheria-like Bacilli. 

Jour, of Med. Res., 1902. 
Zarniko: Zur Kenntniss d. Diphtheriebacillus. Cbl. f. Bakt., vi., 1889. 

See also § 32. 




§ 164. The Bacillus tetani (Kitasato) is a fine, slender bacillus (Fig. 
450 ) which is widely distributed throughout the superficial layers of the 
earth, and is to be regarded as the cause of tetanus. According to ob- 
servations made by Mcolaier in 1885, it is often possible to x^roduce in 
mice, guinea-pigs, and rabbits, by means of subcutaneous inoculation of 
surface -earth, a typical tetanus with fatal termination, 
due to this bacillus. 

It was first demonstrated by Eosenbach in 1886 that 
this same form of bacillus is present in the seat of in- 
jury in cases of tetanus in man following trauma or freez- 
ing ; and that when inoculated into guinea-pigs and mice 
it again produces tetanus. Since that time this discovery 
has been many times corroborated. The bacillus is not yig. 45o.— Teta- 
present in an isolated condition in either the earth or in ^Inaff ^S'^^'^^^x 
the infected wound; and consequently the inoculations i,ooo. 
were made with a mixture of bacteria. Attempts to 
isolate by cultures the bacillus that was regarded as the cause of tetanus 
were unsuccessfully made by many investigators. In 1889, in Koch's 
laboratorj^ Kitasato succeeded in isolating the tetanus-bacillus by^ allow- 
ing the mixed cultures to remain in the incubator for several days and 
heating upon a water-bath at 80° C. for a half -hour or an hour, and then 
subsequently keeping plate -cultures in an atmosphere of hydrogen. The 
bacteria growing in association with the tetanus-bacillus are killed, while 
the tetanus-bacillus is preserved. 

The tetanus-bacillus is anaerobic and thrives very well in an atmos- 
phere of hydrogen, but not in carbonic-acid gas. It grows on ordinary 
peptone-agar that is slightly alkaline, on blood-serum, and in nutrient 
gelatin. The latter is liquefied with evolution of gas. The addition of 
from 1.5 to 2 per cent, grape-sugar to agar-agar accelerates the growth; 
a temperature of 36°-38° C. is most favorable for its development. It 
forms long, thin, bristle -shaped rods which form terminal spores (Fig. 
32 



'602 



THE PATHOGENIC FISSION-FUNGI. 



450 ) giving rise to a spherical swelling at tlie end of the rod (knobbed 
bacilli). In cultures it may form long pseudothreads. The cultures 
give off an offensive odor ; gelatin is slowly liquefied. The bacilli stain 
by Gram's method. They are motile except during the time of spore- 
formation, and possess peritrichous flagella. Pure cultures inocuhited 
into horses, asses, guinea-pigs, mice^ rats, and rabbits cause tetanus, but 
in the case of rabbits larger amounts must be injected. The tetanic con- 
tractures begin in the neighborhood of the point of inoculation. Sup- 
puration does not occur at the point of inoculation. The bacilli cannot 
be demonstrated after the death of the animal, and are never found in 
the tissues except at the seat of inoculation. 

According to experimental investigations by Kitasato, the filtrate of 
bouillon-cultures of the bacilli, which does not contain bacilli, acts in the 
same way as cultures containing the bacilli, and guinea-pigs are espe- 
cially sensitive to it. The blood or transudate from the thoracic ca^ ity 
of an auimal infected with tetanus, although free from bacilli, will cause 
tetanus when injected into mice. It may therefore be assumed tliat in 
tetanus there is an intoxication ^'ith a poison (tetanotoxin) which is diffused 
throughout the blood. This x)oisou is (Kitasato) destroyed by heat (at 
a temperature of 65° C. and over, within a few minutes), and by direct 
sunlight (iu fifteen to eighteen hours), and in diffuse daylight loses its 
virulence within a few weeks. According to investigations of Brieger 
and Cohu the purified poison gives no reaction for albumin, and there- 
fore is not a toxalbumin. 

The infection — intoxication — of man takes place usually through the 
medium of small wounds ; idioi^athic or rheumatic tetanus, which does 
not start from wounds, may arise through infection of the mouth -cavity 
and the respiratory tract (Carbone, Perrero, Thalmann). A preexisting 
catarrh favors the infection (Thalmann). The tetanus-toxin affects 
chiefly the nervous system. 

The Bacillus oedematis maligni ( Vibrion sejytique of Pasteui') is an 
anaerobic bacillus first carefully studied b}' E. Koch. It is present in 
various i)utrefying substances, and is almost never absent from earth 
fertilized, by decomposing fluids or liquid manure. The bacilli are 
3-3.5 ,u. long, and 1-1.1 ,a broad; they often form long pseudothreads. 
They resemble the anthrax-bacilli, though somewhat more slender, are 
rounded at the ends, and not sharjDly cut across. In spore-formation a 
swelling of the rod takes i)lace, as in the case of the Bacillus butyricus, 
so that spindle- and tadpole-shaped forms arise. 

The bacillus is motile, and possesses flagella on the ends as well as on 
the sides. It is not stained by Gram's method. 

It grows in nutrient gelatin as well as in agar and coagulated blood- 
serum, but must be introduced deeply into the medium and protected from 
the air. Nutrient gelatin to which one to two per cent, of grape-sugar 
has been added is an especially favorable medium (Fliigge). Xutrient 
gelatin and blood-serum are liquefied, the latter with evolution of gas. 

The bacillus can be easily obtained by sewing up garden-earth under 
the skin of a guinea-pig, care being taken to prevent the access of air to 
the point of inoculation. The ensuing multiplication of the bacteria 
excites a progressive oedematous swelling of the subcutaneous tissue. 
At a later stage the bacilli spread over the serous membranes, and in- 
volve the spleen and other organs. 

Mice, guinea-pigs, horses, sheep, and swine are susceptible to the 
bacilli ; cattle are not. 



BACIT.LUS PHLEGMONES EMPHYSEMATOSA. 



603 



According" to obsci Vcitioiis by Briefer, Ehrlicb, Chaiiveau, Aiioing, 
and others, the bacilli of malignant c]edenia may also occasionally develop 
in the human body, i)articulai'ly when the tissues are poorly nourished 
and the bacilli through any accident — puncture of a hypodermic syringe 
— get into the deeper tissues. They excite gangrenous processes asso- 
ciated with h^emorrhagic oedema and gas-production. 

As the Bacillus phlegmones emphysematosse R. Fraenkel in 1892 
described an anaerobic bacillus which in many cases is to be regarded as 
the cause of i:)hlegmonous inflammation associated w^ith gas-formation. 
According to Fraenkel the bacillus is motile and only excei)tionally 
forms spores. It occurs in the external world (by Fraenkel it was 
demonstrated upon a splinter of wood with which a man dying of gas- 
phlegmon had been wounded) ; and AYhen injected subcutaneously into 
guinea-pigs or sparrows produces a i3rogressi\'e gangrenous process with 
disintegration of the subcutaneous tissues and muscle, as well as free 
collections of fluid and gas. Intravenous injection into rabbits and 
guinea-pigs is followed by the formation of gas in the internal organs. 

It is x)robable that this bacillus is identical with one described by 
Ernst, \Yelch, and ^siuttall (by the latter as BaciUus aerogenes capsulatus) 
as the cause of foamy liver" (^^ Schaumleber^^) (Ernst) — that is, with a 
bacillus which is regarded as the cause of gas-formation in the human 
liver (Ernst). The condition of foamy organs" {Schaumorgane) prob- 
ably arises (Fraenkel) from the fact that the bacillus in question gains 
an entrance before death into the tissues, into the liver in x^articular. 

Accordingly' to Ydillard and Vi/icent tetanus does not follow the inoculation of teta- 
nus-bacilli deprived of poison. Consequently it must be assumed that the bacilli can 
increase in the tissues of man and animals and lead to poisoning only under certain con- 
ditions, when at the same time the poison of tetanus or of other bacteria (for example, 
BaciUus pnnUf/iosus) gain access totlie tissues. Bl in aenthal holds that the bacilli secrete 
a ferment whicli produces, within the organism, the tetanus poison. 

According to investigations by Kitasato, Tizzoni, Cattani, Baquis, Behring, and 
others, susceptible animals may be made immune against tetanus, or, more correctly, 
may be made poison-proof against the tetanus-poison. The blood of animals thus made 
poison-proof, possesses the power of destroying the tetanus-poison, and consequently 
it is possible to immunize susceptible animals with the curative serum derived from this 
blood, or to cure an attack of tetanus after the disease has already been acquired (cf. § 
32). 

As regards the bacteria of liaimorrhagic infection, see § 44. 

Literature. 

{BueiUus Tetani.) 

Achard: Lesions des nerfs dans le tetanos. Arch, de med. exp,, iv., 1892. 
Babes: Rech. sur le tetanus. Ann. d. I'lnst. de path, de Boucarest, iv., 1893. 
Beumer: Zur Aetiologie des Trisnuis sive Tetanus neonatorum. Zeitsch. f. Hyg., iii., 

1887. 

Blumenthal: Tetanusgift. Zeitschr. f. klin. Med., 32 Bd., 1897. 
Bonome: Ueber die x\etiol()gie des Tetanus. Fortschr. d. Med., 1887. 
Bassano: Origine tellurique du tetanos. Revue de med., ix., 1889. 
Brieg-er: Aetiologie d. Wundtetanus. Deut. med. Woch., 1887; Biol. Cbl., vii., 1887. 
Brieger u. Boer: Toxine d. Diphtheric u. d. Tetanus. Deut. med. Woch., 1896. 
Brieger u. Cohn: Unters. lib. d. Tetanusgift. Zeitschr. f. Hyg., xvi., 1893. 
Carbone e Perrero: Aetiol. d. rheumat. Tetanus. . Cbl. f. Bakt., xviii., 1896. 
Danysz: Toxine tetanique et subst. nerveux. Ann. de ITnst. Pasteur, 1899. 
Engelmann: Serumtherapie des Tetanus. Mlinch. med. Woch., 1897 (Lit.). 
Fermi u. Pernossi: Ueb. das Tetanusgift. Zeitschr. f. Hyg., xvi., 1894. 
Hochsinger : Zur Aetiologie des menschl. Wundstar.rkrampfes. Cbl. f. Bakt., 11, 
1887. 



604 



THE PATHOGENIC FISSION-FUNGI. 



Kitasato: Der Tetanuseneger. Verb. d. XVIII. Congr. d. Deut. Ges. f. Cbir., 1889; 
Deut. med. Wocli., 1889; Tetanusbacillus. Zeitschr. f. Hyg., vii., 1889; Tetanus- 
gift, lb., X., 1891. 

Kitt: Ueber Tetanusimpfungen bei Haustbieren. Cbl. f. Bakt., vii., 1890, 

Kohler: Stand d. Serumtberapie d. Tetanus. Miincb. med. Wocb., 1898. 

Marie: La toxine tetanique. Ann. de I'lnst. Pasteur, 1897. 

Moschcowitz : Tetanus, a Study, etc. (Lit.). Studies from Dept. of Patb. of Colum- 
bia University, 1899-1901. 

Rosenbach: Zur Aetiol. d. Wundstarrkrampfs. Langenbeck's Arab., xxxiv., 1886. 

Roux et Vaillard: Contr. a I'et. du tetanos. Ann. de I'lnst. Pasteur, 1893. 

Thalmann: Aetiologie d. Tetanus. Zeitscbr. f. Hyg., 33 Bd., 1900 (Lit.). 

Tizzoni: Sieroterapia nel Tetano. Mem. della R. Acc. dell' 1st. di Bologna, 1900, 
1901. 

Tizzoni u. Cattani: Tetanusgift. Cbl. f. Bakt., viii., 1890; Arcb. f. exper. PatboL, 
27 Bd., 1890; Widerstandsfabigkeit der Tetanusbacillen. Arcb. f. exper. Patb., 28 
Bd., 1890; Ueber die Arts einem Tbiere die Immunitat gegen Tetanus zu iiber- 
tragen. Cbl. f. Bakt., ix. ; Eigenscbaffcen des Tetanus-Antitoxins. lb., ix., x., 
1891. 

Tizzoni, Cattani u. Baquis: Bakteriol. Unters. lib. d. Tetanus. Beitr. v. Ziegler, 
vii., 1890. 

Vaillard: Immunite contre le tetanos. Ann. de I'lnst. Pasteur, v., 1891. 
Wellner: Tetanus. Ergebn. d. allg. Patb., iii., 1897. 

Wiedenmann: Beitrag zur Aetiologie des Wundstarrkrampfs. Zeitscbr. f. Hyg„, v., 
1889. 



(Bacillus CEdematis Maligni. Bacillus Phlcgmones Empliysematosce.) 

Brieg-er u. Ehrlich: Mabgnes Oedem bei Typbus abdom. Berl. klin. Wocb., 1882. 
Cornevin: Gangrene foudroyante et son inoculation preventive. Rev. de med., viii., 
1888. 

Ernst: Gasbildende Anaeroben u. ibre Bez. z. Schaumleber. Vircli. Arcb., 133 Bd., 
1898. 

Frankel : Ueber die Gaspblegmone, Hamburg, 1893 ; Ueber die Erreger der Gaspbleg- 

moue. Miincb. med. Wocb., 1899. 
Harris, Welcli: ]\torbid Conditions caused by Bacillus Aerogenes Capsulatus. Bull. 

of Jolms Hopkins Hosp., 1900. 
Hesse, W. u. R. : Ziicbtung der Oedembacillen. Deut. med. Wocb., 1885. 
Hibler: Durch anaerobe Spaltpilze bedingte Infectionserscbeinungen. Cbl. f. Bakt., 

XXV., 1899. 

Howard: A Contribution to tbe Knowledge of Bacillus Aerogenes Capsulatus. Welcb 
Festscbrift, 1900; Tbe Origin of Gas and Gas Cysts in tbe Central Nervous System. 
Jour, of Med. Res., 1901._ 

Jensen u. Sand: Ueber malignes Oedem bei Pferden. Deut. Zeit. f. Thiermed., xiii,, 
1887. 

Koch, R. : Zur Aetiologie d. Milzbrandes.' Mittbeil. a. d. K. Gesundbeitsamte, i., 
1881. 

Norris: Infection witb Bacillus Aerogenes Capsulatus. Amer. Jour, of Med. Sciences, 
1899. 

Pasteur: Vibrion septique. Bull, de I'Acad. de med., 1877, 1881. 
Welch u. Nuttall: Jobns Hopkins Hospital Bull, 1892. 

§ 165. The bacillus of bubonic plague (Bacillus pestis) was discov- 
ered in 1894 by Kitasato and Yersin, of the Japanese and French com- 
mission, while investigating an epidemic which had broken ont in Hong- 
Kong. The pest bacillus is a small rod with rounded ends (resembling 
the bacillus of chicken -cholera). It stains easily with aniline dyes, espe - 
cially well with methylene-blue, and in part shows an exquisite polar- 
staining (Fig. 451). It is decolorized by Gram's method. It is found 
in all cases of plague, in especial abundance in the swollen lymph-glands, 
but also in the spleen and blood. It may be cultivated upon the various 
media, and forms bluish -gray colonies, which contain rods of various 
lengths. It multiplies abundantly in bouillon containing sugar, and 
forms toxins. Independent movements have not been observed. Spores 



BACILLUS PESTIS. 



605 



ai-e not formed. The bacilli are easily killed by warming, but are able 
to withstand drying well. 

The bubonic plague, which destroyed great numbers of the inhabitants 
of Europe, at the close of the seventeenth and beginning of the eigh- 
teenth centuries ('^ Black Death ^^), has since 1720 almost disappeared 
from Europe and has shown itself only here and therein Eastern Europe. 
In different countries of Asia (Yunnan in China, Arabia, Mesoi^otamia), 
and in the interior of Africa (Koch) the disease seems to be endemic, 
and spreads from time to time in the same manner as cholera. 

Man is infected usually through the skin, more rarely from the mu- 
cous membrane of the mouth, nose, throat, and conjunctiva, still more 
rarely from the deeper parts of the respiratory tract, although cases of 
primary pest-bronchitis and pest-pneumonia occur. Small wounds usu- 
ally form the avenue of entrance in the skin, but it appears (Albrecht 
and Ghon) that a violent rubbing of an area of the skin with infected 
fingers or clothing may be sufficient to bring about an infection. 

The bacilli are taken up by the lymph-vessels and taken to tlie 
regional lymph- glands, where they cause a very marked swelling of the 
infected gland or group of glands — the primary bubo. Through the in- 
fection of lynii3h-glands situated farther 

along the lymph-system there arise 4/ »^ ^# , ..^^^ ,s% 

mary buboes of the second class, and by ^0% * //^ 
metastasis through the blood stream t ' - L t"^^ 

secondary buboes ar^ formed. The plague •J^ ^, .v*^^ ^| 
is thus characterized in the first place by ^ ^* ' ♦** 

an actcte polyadeyiiUs. Since the poisons ^ "'"^ •* * 

which are in association with the bodies * * * •^•s* ^».. % 
of the pest -bacilli exert a degenerative ? ; / ' \V 

and necrotic effect upon the vessel-walls, ^ *^ m •« '^^^^ f*N 

numerous hcernorrhages are also caused, T C ^ 

and these are absent only in rare cases. - • • 

To these changes there are also added 45i.-piagiie baciiu (fuchsiu). x sso. 
circumscribed foci in the spleen, liver, 

kidneys, lungs, skin, etc. With the exception, therefore, of those cases 
in which the pest-infection is confined to the primary bubo, the disease 
is to be regarded as a geyieral infection (Albrecht and Ghon), which arises 
from the taking-up of bacteria from a primary focus of infection, and 
runs its course with the clinical picture of a polyadenitis and a severe 
hcemorrhagic septiccemia. 

The individual foci are characterized by tissue necroses of the nature 
of coagulation-necrosis (Albrecht and Ghon), as well as by severe exuda- 
tions, inflammation, and hmnorrhage, and are caused by the presence of 
extraordinarily large numbers of bacilli. The lymph-glands of the pri- 
mary bubo show either wholly or for the chief part the appearance of 
hcemorrhagic infarction, and are swollen and of a medullary consistence. 
After the course of a few days they also show yellow necrotic areas which 
later undergo liquefaction. When the disease has lasted longer than six 
days, the liquefaction of the lymph-glands may take on the character of 
a suppuration. 

The tissues in the neighborhood of the lymph-gland are always more 
or less cedematously swollen, infiltrated with blood ; and haemorrhages 
are also found in the walls of the neighboring large veins. 

The secondary inflammations of the lymph-glands and of the lymph- 
adenoid tissue of the mouth and throat do not usually cause such a 



606 



THE PATHOGENIC FISSION-FUNGI. 



marked degree of swelling as do the primary ; they resemble the medul- 
lary swelling occurring in typhoid fever. The surrounding tissues are 
also less changed, but if the process be i^rolonged the picture comes to 
resemble that of the primary buboes. 

The spleen of plague-patients is somewhat swollen, dark red, finely 
granular, shagreened (Albrecht and Ghon), arid often contains small 
necrotic foci, which are caused by the development of the bacilli in great 
numbers. 

In the glandular organs and in the skin, there occur, besides hiemor- 
rhages, also necrotic areas and exudativ e inflammations, all due to the 
presence of bacilli. In the lungs there may occur, in addition to the 
primary pest-bronchopneumonia, secondary metastatic focal inflamma- 
tions and aspiration-bronchopneumonias. 

The majority of individuals infected with pest die within the first 
eight days, but others may live several weeks and then die of marasmus. 

Xot infrequently secondary infections, particularly of streptococci and 
diplococci, are associated with the pest-infection. They arise chiefly in 
the tonsils and follicular glands of the tongue following the changes 
caused by the pest-bacilli (Albrecht and Ghon). 

Among animals, rats, mice, apes, and cats are especiaUy susceptible to 
pest ^ and in these, particularly in rats, spontaneous infections occur, so 
that they may aid in the spread of epidemics. Swine and dogs are less 
susceptible, birds still less so. 

The changes in infected animals agree in general with those observed 
in man. The infection may remain local or become general. After the 
lynii:)hadenitis and the multiple haemorrhages there arise also miliary, 
tubercle-like foci in the spleen, liver, and lungs. The course is usually 
acute, rarely chronic. In the latter case the larger necrotic foci may be 
encapsulated by connective tissue. The animals are easilj^ infected from 
the skin, as well as from the mucous membranes of the intestinal and 
respiratory tracts ; and such infection may take place from an uninjured 
mucous membrane. The inoculation of one mouse confined in a cage 
with other mice may give rise to a cage-epidemic (Schottelius). 

Attempts to immunize animals and man against jief^t by means of dead and attenuated 
pfst-haciUi have been many times carried out, especially by Yersin, Haffkin, m\d Lus- 
tig ; and have been successful in so far that rodents, liorses, and apes have been ren- 
dered immune against inoculations otherwise fatal. According to the reports of such 
attempts in man, a smaller per cent, of inoculated individuals acquire the disease than 
of tliose not inoculated; but doubt is thrown upon the results of these inoculations by 
other authors {Bitter). Further, attempts at immunization and healing have been made 
in man. irifji the sennn of animals irhieh hare been rendered immvne, particularly of 
horses ( I'd ;>///, Lustig); and diHerent authors ascribe to such serum a favorable influ- 
ence. 

During the last several years, as the result of the spread of plague in India and its 
appearance in Europe, numerous articles upon pest have appeared. The most thorough 
pathological anatomical and experimental investigations are those carried out by ^4^ 
Ireclit and Gliurt, whose articles have been used chiefly in the preparation of the text as 
given above. 

Sticker differentiates the following forms of pest according to the first localization 
of tlie bacilli: (1) Bubonic plague (the most common form); {'2) the cutaneous form 
(formation of vesicles and ulcers or furuncle-like inflammations) ; (3) the pulmonary 
form; (4) the intestinal form. 

Some years ago SanareUi ("Sur la fievre jaune," J./?/?, de Vlnst. Pasteur, 1897; 
Cent. f. B'i'kt., xu.) described as the cause of yellow fever a bacillus whose properties 
he sought to determine by means of culture-experiments and animal-inoculations. He 
is still of the opinion that his Bacilbi.s icteroides is the cause of yellow fever (''Zur Lelire 
vom gelben Fieber," Ctd.f. Bakt., xxvii., 1900), and reports favorably of the protective 
and curative effects ("Exper. sur I'emploi du serum curatif et preventif de la fievre 



BACILLUS PESTIS. 



607 



jaune," Ann. de riiist. Pasteur, 1898) of Lis serum obtained from vaccinated animals 
(dogs, horses, cattle). Freire Miin. sur la bacteriologie, patliogenie et traitement de 
la lievre jaune," Rio de Janeiro. 1898, Cbl.f. Bakt., xxvi.) on the other hand opposes 
energetically the correctness of Sanarelli's views, and maintains that the cause of yellow 
fever is a coccus earlier described by him, which he calls the Micrococcus xftiithogenicus. 
By inoculations of the same into dogs, guinea-pigs, and rabbits he was able to produce 
a disease resembling yellow fever, and likewise reports successful protective inocula- 
tions with attenuated cultures. 

Through the investigations of Biicrey, Krefting, and Petersen (cf. Petersen, "Ulcus 
Molle," Arch.f. Derm., xxix., 1894; xxx., 189-)) it is probable that the ulcus moiie or 
soft chancre is caused by a bacillus. This view is, however, opposed by competent 
authors {Finger, "Die Syphilis und die venerischen Krankheiten," Leipzig, 1896); and 
the opinion is advanced that there is no single specific virus of soft chancre. It must 
also be remarked that attempts to cultivate the chancre bacillus have not been success- 
ful. (See also " Observations on the Distribution and Culture of the Chancroid Bacillus, 
by Davis, Jour, of Med. Res., 1902.) 

Literature. 

{Plague.) . 

Abel: Geschichtliches uber die Rattenpest. Zeitschr. f. Hyg., 36 Bd., 1901. 

Albrecht u. Ghon: Ueber die Beulenpest in Bombay im J., 1897, Wien, 1898, 1900. 

Aoyama: Die Pestepidemie im Jahre 1894 in Hong-Kong, Tokio, 1895. 

Babes: Durch Pestbacillen verursachte Veranderungen. Virch. Arcb., 150 Bd., 1897. 

Bitter: Schutzimpfungen gegen Pest. Zeitschr. f. Hyg., 30 Bd., 1899. 

Daubler: Grundziige der Tropenhygiene, Berlin, 1900. 

Dewel: Empfanglichkeit d. Frosche f. Beulenpest. Cbl. f. Bakt., xxii., 1897. 
Flexner: The Pathology of Bubonic Plague. Univ. of Penn. Med. Bull., 1901. 
Gaifky, Pfeiffer, Sticker u. Dieudonne: Pest. Arb. a. d. K. Gesundlieitsamte, 
xvi., 1899. 

Kitasato: Preliminary Note of the Bacillus of Bubonic Plague, Hong-Kong, 1894. 
Koch: Verbreitung d. Beulenpest. Deut. med. AVoch., 1898. 
Kolle: Bakteriologie der Beulenpest. Deut. med. AVoch., 1897. 

Lustig: Gewebsveranderungen bei Beulenpest. Cbl. f. allg. Path., viii., 1897; Siero- 

terapia e vaccinazioni preventive d'ontro la peste bubonica, 1897. 
Markl: Pesttoxine. Cbl. f. Bakt., xxiv., 1898. 
Metschnikoff : La peste bubonique. Ann. de I'lnst. Pasteur, 1897. 
Miiller u. Poch: Die Pest, Wien, 1900. 

Wetter: Le microbe de la peste. Arch, de med. exp., 19C0 (Lit.). 
Nuttall u. Kolle: Die Insekten bei der Pest. Cbl. f. Bakt., xxii., 1897. 
Sata: Aetiologie u. Anat. d. Pest. Arch. f. Hyg., 37. 39 Bd., 1900, 1901. 
Scheube: Pest. Eulenb. Realencyklop., 1897; Die Krankheiten d. w^armen Lander, 
Jena, 1900. 

Schottelius: Die Bubonenpest in Bombay. Hygien. Rundschau, 1901. 
Simond: La propagation de la peste. Ann. de I'lnst. Pasteur, 1898. 
Sticker: Die Pest nacli Erfahr. in Bombay. Munch, med. AVoch., 1898. 
Wyssokowitz et Zabolotny: Recli. sur la peste. Ann. de ITnst. Pasteur, 1897. 
Yamag-iva: Die Bubonenpest. Virch. Arch., 149 Bd., Suppl., 1897. 
Yersin: Sur la peste bubonique. Ann. de I'lnst. Pasteur, 1894, 1897. 
Zettnow: Bacillus der Bubonenpest. Zeitschr. f. Hyg., xxi., 1896. 

§ 166. The Bacillus tuberculosis is the cause of the infections disease 
occnrring so frequently in man and the domestic animals which is known 
ordinarily as tuberculosis, but is also sometimes called pearl disease 
(PerlsucM) in animals. 

The tubercle-bacillus was discovered and thoroughly studied byKocIi 
in 1882. It is a slender rod (Fig. 452), of 1.5-4 // in length, and is 
usually slightly curved. It may be stained by aniline- dyes (fuchsin, 
gentian-violet) to an aqueous solution of which an alkali, or carbolic 
acid, or aniline oil is added. The bacilli when once stained retain the 
stain, even when the preparation is decolorized in dilute sulphuric acid, 
or nitric acid, or hydrochloric acid and alcohol. 

The stained bacilli not infrequently show in their interior clear, shin- 



COS 



THE PATHOGENIC FISSIOX-FUXGI. 



iiig, unstained areas, or are comi^osecl of little stained spherules. Koch 
formerly regarded these clear spots as spores, and this view was generally 
accepted for a long time. Nevertheless, a germination of these struc- 
tures could not be demonstrated, and at the present time they are uo 
longer regarded as spores. Consequently, the tubercle-bacilli form no 
si^ecial resistant forms, but ou the other hand the bacilli are more resist- 
ant against external iufluences, for example, against drying, than are 
many other bacteria. 

The tubercle-bacilli may be cultivated at the body temperature ard 
in the pi'esence of oxygeu wpon coagulated blood-serum, blood-serum- 
gelatin, nutrient agar, and iu bouillon. They iucrease, however, very 
slowly, so tliat only ou the seventh to tenth day or even later, do the cul- 
tures become visible iu the form of dull-white flakes resembling little 
scales. Larger cultures form, ou the surface of coagulated blood-serum, 
whitish, irregularly shaped, lustreless deposits. According to Xocard, 
Eoux, and Bischoff the growth of the bacilli is greatly aided by the 
additiou of giyceriu (four to eight p>er cent.). Pawlowski succeeded in 

cultivating them uj^on potato iu sealed 
glass-tubes. Iu cultures the tubercle- 
bacilli also form threads, which in part 
show brandling. 

At temj)eratures below 28° C. and 
above 4:2° C. the growth of the bacilli 
ceases. Sunlight kills the bacilli iu a 
short time (Koch ). 

If the bacilli from pure cultures are 
inoculated into experimental animals, 
tuberculosis is produced in these; and 
the int>ctiou is transmitted as well by 
inoculatiou under the skin, or ii'to the 
peritoneal cavity, or the anterior cham- 
ber of the eye, as also by inhalatiou of 
au atomized susx^ension of the culture, 
by feediug, aud by injectiou of bacilli into the veius. Guinea-pigs, 
rabbits, cats and gray tield mice are especially susceptible ; dogs, rats, 
aud white mice less so. 

Infection of man and of animals occurs from the taking up of tuber- 
cle-bacilli from the lungs, respiratory iDassages, aud the intestiual tract, 
or from wounds and tissue-ulcerations. In the alimentary tract the 
lymphadenoid apparatus, tonsils, and the intestinal lymph-follicles form 
the most frequent avenue of entrance. Further, a direct transmission of 
the bacilli from the mother to the /(etus in utero, may occur, but this is 
rare. 

The bacilli are spread throughout the external world chiefly by the 
sputa, under certain conditions also by the faeces and urine, further from 
tuberculous ulcers, or from tuberculous organs which are taken from liv- 
ing or dead persons. Since the bacilli are rather resistant, they may be 
preserved outside of the animal body for a long time under certain con- 
ditions, and may become mixed with the respii ed air, as well as with the 
food and drink. The milk of tuberculous cows contains the bacilli es- 
pecially when the udder is diseased ; but the bacilli may also pass into 
the milk when no disease of the udder can be demonstrated (Hirschberg, 
Ernst, Leuch). 

If the bacilli succeed in developing and multij^lying in any tissue of 



\ 



Fig. Tuberrle-bacilli.- Sputum from 

a man suffering wiili pulmonary tuberou- 
losis. >mear-preparation on eover-giass. 
stained witla fuclisiu aud methvleue-blue. 
X 4UU. 



BACILLUS TUBERCULOSIS. 609 

the human body, they lead by a series of clianges to the formation of 
nodular masses of c/rauiilation tissue or tubercles, which remain devoid of 




Fig. 453. Fig. 4.14. 

Fig. 453.— Tissue-changes caused by fresh invasion of tubercle-bacilli. (After Baumgartner-l a. Pro- 
liferating connective tissue ; 7), transverse section of a blood-vessel : c, karyomitoses in connective tissue; 
d, mitoses of an endothelial cell in a blood-vessel; e, emigrated leucocytes, x 350. 

Fig. 454.— Giant-cell containing bacilli, and showing necrotic centre, from a tubercle. Stained with 
gentian-violet and vesuvin, mounted in Canada balsam. X 35U. 

hlood-vessels, and after reaching a certain stage of development undergo 
retrogressive changes. 

The first effect of the development of the bacilli in a tissue is a tissue- 
degeneration, in which (Wechsberg) the tissue-cells as well as the con- 
nective-tissue ground-substance over a larger or smaller area are de- 
stroyed. To the degenerative processes there is added then on the one 
hand an inflammatory exudation — that is, emigration of leucocytes — and 
on the other hand, a proliferation of the tissue-cells remaining preserved 
within the affected area (Fig. 453, «). This is accomplished bykaryomi- 
tosis (c, d), and leads in the connective tissue to the formation of epithe- 
lial-like fibroblasts rich in protoplasm, which are usually designated as 
ep ithelioid cells (a). Since 
the process of cell-divi- 
sion is many times re- 
peated, there arise heaps 
of epithelioid cells («), 
in which the bacilli 
lie iDartly between the 
cells and partly in the 
cells themselves (Fig. 
453). 

Through the prolif- 
eration of the cells the 
remaining connective- 
tissue stroma of the or- 
iginal tissue is pushed 
farther and farther 
apart, so that the indi- 
vidual cells come finally 
to be separated from one 
another only by scanty 
fibres, whose general ar- 
rangement is in the 




Fig. 455. —Tubercle from a fungous granulation of bone (Miiller's 
fluid, Bismarck brown), a, Giant-cell; b, epithelioid cells; c, 
lymphoid cells. X 400. 



610 THE PATHOGENIC FISSIOX-FUNGL 

form of a network, which is conseqiieutlj^ called the reticulum of the 
tubercle. 

The proliferating cells have for the chief part bnt one or two nuclei 
(Figs. 453, a: 455, b), but usually multinuclear cells {giant cells) also 




appear (Figs. 454, 455, a), and these often enclose a very large number 
of large, oval, bladder-shaped nuclei, as well as bacilli. The nuclei of 




Fig. 457.— Large-celled tubercle containlnpr fibrin, from a tuberculous lung (alcoliol, fibrin-stain), a, Fibrin ; 
giant-cell ; c, large-celled tissue. X 3UU. 

the giant cells are almost always irregularly distributed throughout the 
protoplasm of the cell, sometimes grouped in the form of a wreath or 



BACILLUS TUBERCULOSIS. 



611 



Iiorseslloe, sometimes massed at one pole or at two or more points (Figs. 
454 to 459). The non-nucleated portions of the giant cells, when prop- 
erly stained, present conditions of de- 
generation and necrobiosis of the proto- 
plasm, which are brought about hy the 
action of the bacilli present in the giant - 
cells (Figs. 454, 458, c). 

The emigration of leucocytes, which 
may take place even at the beginning of 
the process, accomx3anies also the later 
proliferation (Figs. 453, e, 455, c). 

New vessels are not formed within the 
tubercle; and the old vessels are closed 
through the proliferation of the vessel-walls. 
Usually the 7iew formation of connective 
tissue stops with the production of fibro- 
blasts. 

If a large- celled nodule results from 
the cell -proliferation, the emigration of 
cells leads first to a collection of small round-cells at the i)eriphery of 
the nodule (Figs. 455, c, 450, b), but in part also to an infiltration of 
the same with round cells, which may be so marked that the large cells 
are either partly or wholly concealed, and the picture presented is 
that of a small- celled tubercle. If the emigration of the cells at the very 
beginning is very abundant the tubercle assumes from the start the char- 




FiG. 458.— Caseous necrosis of tubercu- 
lous granulation tissue (alcohol, fuchsin, 
aniline blue), a. Granular, Oi, lumpy case- 
ous masses ; 7), fibrocellular tissue : c, giant- 
cell with bacilli; d, bacilli in cellular tissue; 
f , bacilli in necrotic tissue ; /, bacilli en- 
closed in cells, x 200. 




Fig. 



459.— Section of miliary tubercle of tlte omentum (alcohol, hEemutoxylin, eosin). a. Caseous centre 
containing remains of fat-cells ; b, fibrocellular periphery ; c, giant-cells ; d, fat tissue. X 100. 



acter of a small-celled focus, though mononuclear fibroblasts or giant-cells 
maybe demonstrated in the focus without much difficulty (Fig. 456, b). 

A serous exudation is also usually associated with the cellular emi- 
gration, ^\\{\ fibrin may be formed both toithin the tubercle itself (Fig. 457, a) 
and in its neighborhood. 



612 



THE PATHOGENIC FISSION-FUNGI. 



At the height of its development the tubercle forms a small, gray, 
translucent cellular nodule, which may reach the size of a millet-seed, aiid 
encloses in its tissue tubercle-bacilli in larger or smaller numbers. When 




Fio. 460.— Fibrocaseous tubercle of the lung (alcohol. Van Gieson's). a, ('a^.cous centre; thick, 
homogeneous connective tissue poor in nuclei ; c, connective tissue rich in cells ; d, lung tissue. X 8U. 



it has reached a certain size retrogressive changes usually appear in its 
centre, the tubercle in consequence becoming cloudy, opaque, and of a 



Ct' 



Fig. 461.— Fibrous tubercle in the thickened synovial membrane of the knee-joint (alcohol, hteinatoxylin, 
picric acid, fuchsin). a. Connective tissue ; c, d, fibrous tubercle. X 75. 

white or grayish-white or yelloivish- wJiite color — these changes being desig- 
nated as caseation. 

The caseation of the tubercle is dependent on the one hand upon a 



TUBERCULOSIS. 



613 



necrobiosis of the cells, and on the other upon the deposit of coagulated sub- 
stances in the spaces between the cells. The cell-necrosis is characterized 
by a loss of the nuclei and a transformation of the cells into lumpy 
masses which later disintegrate and become granular (Fig. 458 a^, a). 
The deposit between the cells consists either of a network of fibrin (Fig. 
457, a) or of a granular or hyaline reticulated fibrinoid substance resem- 
bling fibrin but which does not take the Weigert's fibrin stain and is 
stained yellow by Van Gieson's. In the further course of the process of 
caseation the fibrin and fibrinoid substance disintegrate into a granular 
mass which fuses with the cell -detritus, so that the central j)art of the 
tubercle consists of a lumpy granular mass (Figs. 459, a, 460, a) which 
takes a weak diffuse stain with nuclear stains. 

The caseation affects at first the central i)ortion of the tubercle, and 
is usually confined to this, while connective tissue is formed at the per- 
iphery, so that the tubercle comes to consist of a caseous centre (Fig. 
459, a) and ^ fibrocellular periphery (b) which usually contains giant-cells. 
Under certain conditions the caseation may involve the entire tubercle. 
If the caseation does not affect the periphery, the fibrocellular tissue of 
the peripheral zone, sooner or later, becomes transformed into a pure 
fibrous tissue, so that a fibrocaseous tubercle (Fig. 460, a, b) is formed, 
the connective tissue of which is coarsely fibrillar or hyaline and i^oor in 
cells (&), and in the course of time usually becomes sharply defined from 
the caseous centre {a), so that the latter appears to be encapsulated by 
connective tissue. If the tuberculosis runs a favorable course the cen- 
tre instead of caseating may undergo a connective-tissue metamorphosis 
(Fig. 461, b, c, d), so that the tubercle becomes changed into a fibrous 
nodule. 

The i)ifectious nature of the disease known as tiiberctiloaiH hud ah'cady heeu deter- 
mined by the experimental transmission of tuberculosis to animals {Villeiuin, Lebert, 
Wyas, ColmJieiin, Klehs, Langhans, and others), before the discovery of the tubercle- 
bacillus. Nevertheless, it was a long time before the view that tuberculosis was an 
infectious disease received general acceptance, and opposition to this view has even to- 
day not wholly disappeared {Middendorp). 

The peculiar behavior of the tubercle-bacillus toward stains — that is, its property 
of retaining the stain after treatment of the preparation with acids and alcohol, the so- 
called acid- and alcolioUresistance — makes it possible to demonstrate with relative ease 
the presence of tubei'cle-bacilli in the sputum or in the tissues, and to differentiate it 
from other bacteria. It should be noted, however, that other bacteria show these prop- 
erties; the bacillus of leprosy, the sinegina-bacillus (a bacillus very frequently found on 
the corona glandis, between the scrotum and thigh and in the folds between the labia 
majoraand minora), further tw^o different bacilli found in butter {one Cie^crihe&hy L. Rab- 
inowitsch and Petri, the other by Korn), and finally also different bacilli cultivated by 
Mueller from grasses (timothj^-grass) and from cow-dung. All these acid-resisting bacilli 
may under certain conditions lead to errors of diagnosis; for example, the smegma- 
bacillus in the examination of urine, the butter-bacilli in the examination of butter, the 
latter particularly, since the bacillus described by Rabinoiritsch, when injected into the 
peritoneal cavity of guinea-pigs, causes a disease of the abdomen similar to true inocu- 
lation-tuberculosis, while the bacillus described by Korn causes a pseudotuberculosis in 
white mice (these animals showing but slight susceptibility to true tuberculosis). 

Since the tubercle-bacillus in cultures forms simple and branching threads {Klein, 
Fischel, Coppen-Jones, JSocard, Maffucci, and others) and bud- and clvib-like swellings, 
many authors are inclined to group it with the thread-fungi. Lehmann and JS'eumann 
designate it as Myobacteriuni tuberculosis, Coppen-Jones as Tuberculomyces. 

Since the tubercle-bacillus in caseous pulmonary foci {Coppen-Jones), and after 
direct injection into the parenchyma of the brain, kidneys, mammary glands, and testi- 
cles, as well as after the intra-arterial injection of large numbers of bacilli {Babes, Lem- 
diti, Schulze, Lubarsch, Friedrich, and jS'dsske) forms, in addition to the ordinary colonies 
of bacilH, fungus-masses also resembling those of actinomyces, on the outer surface of 
which ray-like clubs radiate into the suriounding tissue, Lubarsch and others, in the 
assumption that the fungus-masses consist of branching threads, have classed the 



614 



THE PATHOGENIC FISSION-FUNGI. 



tubercle-bacillus with the {letinotnyces or ray-fungi. Ijihursrli icuanls the ray-fungi 
as a sub-class of the Streptothiirt.'^, an intcrnicdiatc izioii]) lyin^- Ix'tween the ,'<chizo- 
mycetes and the llyiihoinycetefi, and charaetei'i/.ed l)y the formation of (•lul)s; and to this 
class he assigns also the buttei'- and dung-fungi in('ntioned aljovc. According to Fried- 
rich and JS'osske the fungus-masses regarded as resendjling tliosc of actinonnces consist 
only of rods. 

According to the investigations of ILini inerschhKj, llnppd, Sata, and others, the 
tubercle-bacilli contain an abundance of fat, which under proper conditions may be 
demonstrated by staining with sudan (Sata). According to ILdiuiwrsrlihig tlie tubercle- 
bacilli contain twenty-seven per cent, of substances soluble in alcohol and ether (fats, 
lecithin, poisonous substances), while other bacteria contain only 1. 7-10 per cent, of the 
same. The remaining substance insoluble in alcohol contains albumin and cellulose. 

According to the investigations of Fnidden, JIode/ij)//L Ko.stt n it.scJi, Vissmann. Ma- 
sur, Kockel, and others, dead tubercle-bacilli, when introduced into the tissues of an 
animal by inoculation, or injection into the blood-stream, or through introduction inta 
the respiratory passages, excite, at the point of deposit, inflammation and tissue-pro- 
liferation similar to that caused by living bacilli, and in the case of a large inoculation 
may lead also to suppuration. These changes differ, however, from those i)]-oduced by 
living bacilli, in that the bacilli are destroyed after a few wrecks and the nodules of 
granulation tissue heal through a transformation into fibrous tissue; and further, by the 
fact that the severity of the local tissue-proliferation is dependent wholly upon the 
amount of dead bacilli introduced, and that there is no spread of the process throughout 
the body. The dead bacilli must therefore contain substances (proteins) which cause 
inflammation and later also tissue-proliferation. 

In addition to the local effects, the substance contained in the cell-bodies of the 
bacilli may also cause emaciation of the animal 

The active substance of the bodies of the bacilli — tuberculin — was first produced by Koch 
(1S90) from six- to eight-weeks-old cultures in a weak alkaline veal-infusion, to which 
one per cent, of peptone and four to five per cent, of glycerin were added, by evapor- 
ation upon a water-bath to one-tenth of the original volume and filtering through a 
filter of earthenware and silicious marl. Later (1897) he dried highly virulent cultures 
of tubercle-bacilli in a vacuum-exsiccator, then triturated the diy substance, mixed it 
with distilled water and centrifugated it. The active principle is contained in the 
muddy precipitate thus obtained, which is again di'ied and triturated and dissolved in 
water to which twenty per cent, of glycerin is added for the pui-pose of preservation. 
This tuberculin (designated by Koch as T. R.) is said to contain 10 mgm. of solid sub- 
stance in 1 c.c. (prepared by Meister, Lucius, and Bri/nuinf/). 

Tabe, by treating tubercle-bacilli killed by heating, with alcohol, ether, potassium 
hydroxide, and the Schweizer reagent (copper oxide-ammonia, solvent of cellulose), 
olDtained three substances: fat, an albuminous body which lie called tuberculo-rnycopro- 
tein, and a substance whose chemical nature was not definitely determined, which he 
called tuberculo-bactericidin. 

Mycoprotein, when injected subcutaneously, causes a collection of leucocj'tes ;• 
large doses kill guinea-pigs in two to four days. Tuberculo-bactericidin also causes 
local inflammation; but is less poisonous for the organism as a whole. 



Literature. 

{Tubercle -hacUli and Formation of Tubercles.) 

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Arnold: Anatomie d. miliaren Tuberkels. Virch. Arch., 83 Bd., 1880. 

Auclair: Les poisons du bac. tuberculeux. Arch, de med. exp., 1899. 

Babes u. Proca: Wirkung d. Tuberkelbacillen. Zeitschr. f. Hyg., xxiii., 1896. 

Baumgarten: Tuberkelbakterien. Cbl. f. d. med. Wiss., 1882, 1883; Tuberkel u. 

Tuberkulose. Zeitschr. f. klin. Med., xi., 1885; Diagn. tuberk. u. syph. Processe. 

Wien. med. Woch., 1900. 
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Carriere: Alterat. du foie et des reins prod. p. 1. toxines tub. Rev. de med. exp., 

1897. 

Colinheini u. Frankel: Uebertragbarkeit d. Tuberkulose. Yirch. Arch., 45 Bd., 
1869. 

Cornet: Die Tuberkulose, Wien, 1899. 

Czaplewski: Nachweis der Tuberkelbacillen im Sputum. Cbl. f. Bakt., viii., 1890. 
Dobroklonski : Developp. de la tuberculose experim. Arch, de med. exp., ii., 1890. 



TUBERCULOSIS. 



615 



Ernst: How Far may a Cow be Tuberculous before her Milk becomes Dangerous as 

an Article of Food? Amer. Journ. of Med. Sc., 1889. 
Falk: Exudative Vorgange bei d. Tuberkelbildung. Vircli. Arch., 139 Bd., 1895. 
Ferran: Neue Eutdeck. bezligl. d. Bac. d. Tuberkulose. Wien. kliu. Woch., 1898. 
Fischel: Ueber die Morphol. u. Biol. d. Tuberkulose-Erregers. Fortschr., x., 1892, 

VVieu, 1893. 

Fischer: Uebertrag. d. Tub. durcli die Nahrung. Arch. f. exp. Path., xx., 1886. 
Fliig-g-e; Die Verbreitung der Phthise. Zeitschr. f. Hyg., 30 Bd., 1899. 
Fraenkel: Smegmabacillen. Cbl. f. Bakt., xxix., 1901. 

Friedrich u. Ndsske: Localisirung der Tuberkelbacilleu. Beitr. v. Ziegler, xxvi., 
1899. 

Glinther: Bakteriologie, Leipzig, 1898. 

Hammerschlag : Bakteriolog.-chem. Unters. iiber Tuberkelbacillcn. Cbl. f. klin. 
Med., 1891. 

Hering: Studien iiber Tuberkulose, Berlin, 1873. 

Hirschberg-er : Infectiositat d. Milch tuberkuioser Klihe. Deut. Arch. f. klin. Med., 
44 Bd., 1889. 

Jani: Tuberkelbacillcn in gesunden Geweben bei Lungenschwindsucht. Virch. Arch., 
108 Bd., 1886. 

Johne: Die Geschichte der Tuberkulose, Leipzig, 1883. 

Jones; Morphologic u. system. Stellung d. Tuberkelpilzes. Cbl. f. Bakt., xvii., 1895. 
Kastner: Beitr. z. Infectiositat des Fleisches tuberkul. Kinder. Munch, med. Woch., 
1889. 

Klebs: Impf versuche. Virch. Arch., 44, 49 Bd. ; Arch. f. exp. Path., i., x., xvii.; 
Prag. med. Woch., 1877. 

Koch: Die Aetiologie der Tuberkulose. Berl. klin. Woch., 1882, Xo. 16; 1883, Ko. 
10. Verh. d. Congresses f. inn. Med., Wiesbaden, 1882; Mittheil. a. d. Kais. 
Gesundheitsamte, ii., Berlin, 1884; Mittheil. lib. ein Heilmittel geg. d. Tuberku- 
lose. Deut. med. Woch., 1890; Mittheil. fiber das Tuberkuhn. lb., 1891; Neue 
Tuberkulinpraparate. lb., 1897. 

Kockel: Histogenese des Miliartuberkels. Virch. Arch., 143 Bd., 1896 (Lit.). 

Korn: Saureteste Bakterien. Cbl. f. Bakt., xxv., 1899, xxvii., 1900; Bacillenbefunde 
in der Marktbutter. Arch. f. Hyg., 66 Bd., 1899. 

Kostenitsch : De revolution de la tuberculose par les bacilles morts. Arch, de med. 
exp., v., 1893. 

Kostenitsch et Wolkow: Rech. sur le developp. du tubercule. Arch, de med. exp., 
iv., 1892. 

Koster: Ueber fungose Gelenkentzlindung. Virch. Arch., 48 Bd,, 1869. 
Langhans: Die Uebertraguug der Tuberkulose auf Kaninchen, 1868; Riesenzellen 

mit wandstiindigen Kernen in Tuberkeln. Vircli. Arch., 42 Bd., 1868. 
Lebert u. Wyss: Uebertragung d. Tuberkulose. Virch. Arch., 40 Bd., 1867. 
Leuch: Hygien. Miichcontrole. Correspbl. f. Schweizer Aerzte, 1896. 
Levene: Biochemical Studies on the Bacillus Tuberculosis. Jour, of Med. Res., 1901. 
Lubarsch: Zur Kenntn. d. Strahlenpilze. Zeitschr. f. Hyg., xxxi., 1899. 
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nertuberkulose. Zeitschr. f. Hyg., xi., 1892. 
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Metschnikoff : Die phagocytare Rolle der Tuberkelriesenzellen. Virch. Arch., 113 

Bd., 1888. 

Middendorp : La cause de la tuberculose, Groningen, 1897. 

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Nocard et E-oux: Bacille de la tuberculose. Atti. de ITnst. Pasteur, xi., 1897. 

Orth: Exp. Unters. liber Fiitterungstuberkulose. Virch. Arch., 76 Bd., 1876. 

Pawlowsky : Culture des bac. de la tub. sur la pomme de terre. Ann. de I'lnst. Pas- 
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Predohl: Die Geschichte der Tuberkulose, Hamburg, 1888. 

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fection of Dead Tubercle Bacilli. New York Med. Journ., 189L 

Prudden and Hodenpyl: Action of Dead Bacteria in Living Body. New York Med. 
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Plitz: Die Bezieliungen d. Tuberkulose d. Menschen zur Tuberkulose d. Thiere, 
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Rabinowitsch : Zur Frage d. Vork. v. Tuberkelbac. in d. Marktbutter. Zeitschr. f. 
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616 



THE PATHOGENIC FISSIOX-FUXGI. 



Rabinowitsch 11. Kempner: Infectiositat d. 3Iilcli tnberk. Kulie. Zeitsclir. f. Hv'^. 
xxxi.. 1S99. 

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genscliwindsucbt. Beitr. v. Ziegler, xvi.. 1894. 
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Wocli., 1884: Zusammenfass. Bericbt lib. d. Aetiolosie der Tuberkulose. Cbl. f. 

Bact., iii.. 1888. 

Welcker: Pliagocytare Rolle d. Riesenzellen. Beitr. v. Ziegler, xviii.. 1895. 
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Yersin: Etude sur le developpement du tubercule exper. Ann. de ITust. Pasteur, ii., 
1888. 

Ziegler: Ueber die Herkunft der Tuberkelelemente, Wiirzburg, 1875; L'eber patholog. 
Bindegewebs- u. Gefilssneubilduno:, Wiirzburs:. 1876; Tuberkulose. Eulenbiirff's 
Realencyklop., xxiv., 1900 (Lit.). ^ 

§ 167. Tuberculosis is at the beginning a local disease, which occurs 
most frequently in the lungs, intestinal tract, and skin : that is, in places 
accessible from without. Cases of cryptogeiuc infection are by no means 
rare ; in these the first demonstrable disease-changes appear in tissues 
concealed in the deeper portions of the body-x^arenchyma — as, for exam- 
ple, in the lymph-glands, adrenals, bones, joints, brain, tubes — and it is 
to be assumed that under certain conditions the bacilli enter the body 
without causing lasting changes at the point of entrance, so that they 
develop first in some distant organ to which they are carried by the blood 
or lymph, and through multiplication give rise to tissue-proliferation and 
to emigration of white blood-cells. 

The local disease usually begins with the formation of miliary tu= 
bercles — that is, cellular nodules of the kind described above — which 
arise iu the tissue either singly or (in case of multiple infection) in great 
numbers simultaneously, or one after another (secondary dissemination 
of the multiplying bacteria). The tissue in the neighlDorhood of the 
individual tubercles, as well as that between the tubercles, shows some 



TUBERCULOSIS. 



6ir 



times a more, sometimes a less pronounced appearance of inflammatory 
exudation and proliferation of an especiallj^ cellular type ; and through 
these processes there are frecxuently formed large granulation=areas in 
the infected connective tissue. 

In the case of a surface colonization of the badlU, as is possible in the 
alveoli of the lung and in the smallest bronchioles, an exudative catarrhal 
inflammation may be the first sign of the infection, while proliferative 
processes in the connective-tissue stroma and in the pulmonary vessels 
appear only at a later period. 

In the mucous membranes and in the skin (Fig. 462) large areas of 
the mucosa and submucosa, or corium respectively, may through the 



1 



4cf 



Fig. 462.— Lupus of ttie skin with atypical growth of epithelium, from the region of the knee Calcohol, 
hsematoxylin, fuchsin, picric acid), a, Corium converted into granulation tissue in which tliere are scat- 
tered tubercles ; b, epidermis ; c, epithelial plugs growing into the deeper tissues ; d, tubercle. X 50, 



formation of such granulations undergo a nodular or a diffuse flattened 
thickening. In the serous membranes there may develop large, flattened 
nodules in whose neighborhood the serosa is thickened and covered with 
a fibrinous exudate. In the synovial membrane of the joints and burs^e 
there often arise soft, spongy proliferations, the so-called fungous granu- 
lations (Fig. 463) ; in the periosteum and bone-marrow round, grayish- 
red, or gray granulation -areas of varying size appear. All these areas 
have one feature in common — namely, in their neighborhood are found 
inflammatory infiltrations and proliferations of tissue, which bear the 
character of a granulation tissue (Fig. 462, a ; 463, b) inclosing charac- 
teristic non-vascular, cellular nodules — tubercles (Figs. 462, d ; 463, c) 
— which often contain giant-cells. In grayish-red tissues rich in blood 
the tubercles may often be recognized by the naked eye as gray, or, when 
undergoing caseation, as white or yellowish -white nodules.' 

The area of tuberculous granulation tissue when once formed becomes 
larger in its further course of development by an ajypositional groivth, 



618 



THE PATHOGENIC FISSION-FUNGI. 




Fig. 463.— Tuberculous prranulation tissue from 
the synovial -meinbrane of the knee-joint (Muller's 
fluid," Bismarck lirnwn). a. Connerrive tissue; h, 
granulation ti^^sm- ; c tubercle. X 80. 



dense fibrous tissue (Fig. 
raugemeut (a), aud in 
part is more lij aline and 
homogeneous in char- 
acter. In the lungs such 
connective-tissue nodules 
contain more or less car- 
bon-pigment (Fig. 466). 

A second form of ter- 
mination is a combina= 
tion of caseation and 
fibrous induration com- 
prising dense fibrous tis- 
sue (Fig. 467, h, d) and 
caseous foci («) of vary- 
ing size. 

The third termination 
consists essentially in 
caseation, the tubercu- 



whereby the same processes, as just 
described, consummate them.selves 
at tJie periphery. There may arise 
in this way, either within an in- 
fected organ, or upon the surface 
of such, nodules of large size, soli= 
tary tubercles (Fig. 464, c) as, for 
exam})le, in the inn, brain, and 
ux^oii the dura mater, which not 
infrequently resemble true tumoi'S, 
saicomata in particular. Furthei*, 
the tissue tran.sformed by the tu- 
berculous process or the newly 
formed tissue respectively, may 
sulfer various fates ; and there ma^' 
be distinguished three chief forms 
of termination, which may, how- 
ever, be combined in various ways. 

In a first group of cases the 
production of connective tissue 
forms the most striking featui-e, 
and there results a connective= 
tissue induration of the diseased 
tissue (Fig. 465) with the develop- 
ment of a dense, fibrous connective 
tissue (a). If the process does not 
come to a standstill, there may 
be fonnd in association with the 
fibrous tissue new proUferations of 
granulation tissue (b), and often also 
a larger or smaller number of typi- 
cal tubercles (c). If the process 
comes to a complete standstill and 
to a cure of the infection, the en- 
tire area may come to consist of a 
466, a, b) which in part shows a nodular ar- 
b 




Fig. 464.— Large solitary tubercle of the pia mater of the cerebel- 
lum in vertical section, a. Cerebelhim: l>. dura mater adherent to 
the tuhnrcle : c. lauiinaterl tubercle : gray periphnral zone 
adherent t^ tlip dura mater and beset with yellowish-white, nod- 
ular deposit>. Natural size. 



TUBERCULOSIS. 



619 



I0118 gniiiiiLitioii tissue djiiig and x)r()diiciiig- 110 connective tissue at all, 
or only in such a slight amount that it is completely overshadowed by 
the caseous masses (Fig. 468 J. 

Both the tibrocaseous and the purely caseous areas may become 



I 

I 



GT 



Fig. 4U5.— Tul)eR'ul()iisiiKlurati()U of the lung (alcoliMi. luem itM.wlin, ami eosiii). o, L'ense, fibrous tissue; 
/^ cellular granulation li^sur; i-, L:-i:int-cclls. >; 40. 




Fig. -iOtj.— Tuberculous induration of the lung (alcoiiol, liaMuatoxvlin, eosin). a, Homogeneous fibrous 
nodules poor in cells and in part pigmented ; 7>, diffuse induration of the lung. X 24. 




r 
t 




620 



THE PATHOGENIC FISSION-FUNGI. 



healed, through their encajhsuJationfrom the ,snrrounding tissues by connec- 
tive tissue (Figs. 467, b : 468, e, ej. Such a liealing can be regarded as 
complete ouly when in the connective-tissue capsule (Fig. 468, e, e) aud 




Fig. 467.— Encapsulated area of casentton of the lung with induration and eruption of tubercles In the 
neighborhood (formalin, alcohol, hiTeuiatoxvhn, eosin). a. Caseous area; J), fibrous capsule ; c, tubercle; 
c7, indurated lung tissue ; e, area of grainilation tissue. • X 40, 




tubp:rculosis. 



621 



its neighborhood («) neither fi-esh grannlation-tissne areas nor tubercles 
are still present. Occasionally calcification of the encapsulated caseous 
mass may occur as a further sign of the termination of the process. 

The caseous masses of tuberculous foci are sometimes firm, some- 
times soft, and in the latter case very often suffer a disintegration and 
liquefaction leading to the formation of milk-white, crumbling, and pul- 
taceous or even thin fluid masses, so that the tuberculous area comes to 
present the picture of an abscess surrounded by a wall (designated as 
cold ahscess). Eupture and emptying of the same externally leads to the 




Fig. 469.— Tuberculous cavern in the tibia (alcohol, picric acid, hasmatoxylin, carmine) . Transverse 
section, a. Periosteum ; b, rarefied cortex ; c, periosteal deposit of bone ; d, fibrous tissue on the inner 
surface of the cortex ; c, granulation tissue containing tubercles ; f, sequestrum with bony trabeculae, 
infiltrated with granulation tissue; g, union of the granulation tissue with the sequestrum : lu cavity that 
had been filled with pus and caseous masses. X 3]^. 

foimatioii of cavities or caverns and fistulous passages accessible from 
without, and, when there is a wide opening, to ulcers. 

Disintegration and cavity -formation occur x^articularly in the lung, and 
may there lead to the formation of cavities as large as a man's fist or 
larger. They also occur not infrequently in caseating lymph -glands, and 
,in caseous foci in the kidneys, brain, muscles, vSkiu, and bones (Fig. 
469). The cavities (/« ) contain in the beginning the liquefied tuberculous 
tissue, in which not infrequently remains of the original tissue may be 
recognized in the form of sequestra (/)• After the evacuation of the 
contents the wall may furnish material sufficient to fill the cavity again 
either through the secretion of pus or through the breaking-off of necro- 
tic tissue. Hcemorrhages not infrequently arise through the erosion of 
blood-vessels. 

The icalls of the caverns and abscesses are usuallj^ lined by caseating 
granulation tissue containing tubercles (Fig. 469, e) ; the surrounding 
tissue becomes indurated in ]3art, and in part the seat of caseating foci. 



62-2 



THE PATHOGENIC FISSIOX-FUNGL 



J leers occur most lVc(|nciitly in the iiiucons inenibranes (Fig. 470, /?) 
and in the skin, since tlie sot'iening caseous masses in these regions most 




Fi(4. -iTO.- Tiilieivuliius ulrt^r df tlin intesiine ^vitll eniiiTirm of Tubercles in ilie in-ieiiViMrli i a'..- ■'r.n], 

Bismarck brown I. ((, Mucosa: -ubmur. isa : <•. iaus<-ularis interna : '7. nuiscularis exTe-rnn -^i-' sa ; 
-.'liTai-v fi.niclo; mucosa intiltratetl witli cells: //. ulcer: //j. area of softening: i. recent, /j. caseous 

tuo.-:r!M. ai. 



frequently break through to the 

are sm-rounded V>t ? 
tissue, often also containing tubercles 



urface. The edues and base of the 



ulcers are sm-rounded by an inflammatory zone of inhltrated granulation 







Fig. 471.— Besrinnine tuberculosis of the lunar with 'Ut catarrh alcnh"l. orcein', a. Caseous area with 
remains of elastic tisstie : h. normal luncr Tissue \ r. pleura with Tubercles ■ <K t . tubercles in the neighbor- 
hood of the caseous area: t. tubercle in the jileura : periarterial. //. peribronchial. /, perivenous 
tubercles of the lymph-vessels: /.-. new-f. .nnat;. 'U -f iiiioiu> ti><ue beneath the limiting elastic layer of the 
pleura. )\ 16. 



TUBERCULOSIS. 



Gl>3 



If a tuberculous focus does uot l^econie liealed tlu'ouo-h tissue-iudu- 
ratioii, sequestration or encapsulation of the dead tissue, or through the 
removal or death of the bacilli, there exists the danger of metastasis. 

This takes place first by the h inph-chainiels ; and a x)art of the i^ict- 




Fig. 472.— Beginning tuberculosis of the lung In a two-year-old i-liild. Horizontal section through the 
right lung (Miiller's tiuid, carmine), a. Caseous area in the region of the anterior border; &, posterior 
Inner border free from tubercles; c. transverse section of the bronchus ; d. r/j, caseating lymph-glands ; e, 
pulmonary vein ; f. point where the vein t' has become adherent to the lymph-gland c7] ; cheesy degenera- 
tion of the vein-wall has also begun at the same point ; g, tubercles in the Ij-mph-vessels of the pulmonary 
parenchyma; h, periarterial, i, peribronchial, /f, perivenous, /, pleural tubercles; m, tubercle of lymph- 
vessel at hilum of the lung. X 2>b. 



624 



THE PATHOGENIC F18SI0X-FUNGI. 



lire of a progressive tuberculosis is the development of tubercles in the 
lymph-spaces and in the walls of the lymph- vessels (Figs. 470, i, ; 471, 
e, f, g, h, i; 472, g, h, i, k, I, m) in the neighborhood of the primary 
focus. The lymphogenous miliary tuberculosis is in some cases limited 

to the immediate neigh- 
M , J- ^ , borhood of the primary 

fi^#'?^f^%:.f.i"/;. , focus (Fig. 471), at other 

Vl-^^ ¥ ci^'^.^f^"' times it involves larger 

"^^^i ^ . ' " areas and may, for ex- 

-^^^^ V 1^'^'^ ample, extend from a 

f£ / ^^^''^c ^ . caseating tubercle in the 

~ ^ ^ ^ l^iig (Fig. ^:2, a) over a 

^el^o^/ ^^"^ " '^'^f'r*^? l^^g^ P^^^^t pulmo- 

I 'C*<ft.fe^Je"oV^^® ^V' r ^^^^^y lymphatic system. 

* .\4T-'4'l^'f ^'"^^ ' T^^^^ lymphangiotic tu- 

bercles present the ap- 
^ " * pearauce of bright graj' 

^ jT^ "r nodules, often surrounded 

c -^ : .t^ffe ^ c P Gcsg^* by a red zone, and consist 

l-%5>/4tV!| essentially of the same 




^ ' structure as the primary 

1^^^^ -^^^Y-^^S lymph-glands 

-^^ ^ ^ / ^ 7 /' ' ^ may be affected very early 

472, d, Vhere- 

FiG. 473.— Eruption of tubercles in a Ivinpli-gland (alcohol, K^,,«l^c /^l^-r^^l^-r^ 

htematoxylin). o. Tubercle ; (h- caseous tubercle : tissue of the UpOU lUDei CiCS CIC^ ClOp lU 

Ivmph-gland ; c, Riant-cell in the centre of a tubercle ; Cj, giant- them TFip" 47S CI n ^ 

cell at the edge of a caseous focus ; d, large-celled tissue between : 77 ^ ^ • '^i 7' 

the tubercles ; e, blood-vessel. X 150. leading through SUCCCS- 

sive croiDS of the same to 
a more or less marked enlargement and finally to a caseation of the 
glands (Fig. 472, d, d^), or to an induration, or to a combination of these 
processes. The thoracic duct may become infected from caseating and 
disintegrating lymph -glands, and through this channel an infection of 
the blood may also take place. 

Yery often the formation of metastases ta'kes place also through the blood- 
stream ; in the first place by the entrance of bacilli through the lymph 
from the thoracic duct as mentioned above, but very often also as the 
result of the direct erdrance of bacilli into the circulating blood. In tubercu- 
lous tissue the bacilli may pass directly into small veins, though the 
obstruction to the circulation due to the closure of the vessels usually 
prevents their further dissemination. Often enough the bacilli gain 
entrance into the larger veins — as, for example, through the adhesion of 
caseating h^mph-glands at the hilum of the lungs (Fig. 472, dj with the 
neighboring veins (c^f), the tuberculous process involving the vein- walls 
by direct extension. Moreover, an infection of numerous veins^ith tuber- 
cle-bacilli may occur in the neighborhood of a tuberculous focus, so tliat 
the small veins of an entire vascular system may present a well-marked 
tuberculous disease — that is, an inflammatory granulation-proliferation 
of the vessel-walls with the formation of tubercles and subsequent case- 
ation (Fig. 474, b), so that, if thrombosis does not occur, large numbers 
of bacilli may enter the blood-stream from the diseased walls. In rare 
cases the arteries, particularly the pulmonary arteries, m^y become 
tuberculous through infection from the surrounding tissues, and so may 
give off bacilli to the blood-stream. 



TUBERCULOSIS. 



625 



The transportation of the bacilli throngh the blood-stream gives rise 
to a hsematogenous miliary tuberculosis — that is, to an eruption of 
miliary tubercles (Fig. 475, a) at those places where the bacilli become 
lodged and multiply. Just where these places will be, and how numer- 
ous the tubercles, depend upon the location of the point of rupture and 
the number of bacilli entering the blood. The entrance of many bacilli 
into the blood may lead to a general hcematogenous miliary tuberculosis. 

If the bacilli have entered the blood-stream in small numbers and 
have been deposited in only one organ, and if death does not ensue, there 
arises in this organ a progressive hcematogenous local tuberculosis, which 
runs a course similar to that of the primary focus coming from without. 

The inflammation accompanying the hcematogenous eruption of tubercles is 
sometimes more, sometimes less pronounced, and is usually most severe 
in the meninges and in the lungs. 

Should a tuberculous focus in the lung break into the bronchi, as the 
result of the softening of a caseous area, or if a caseating focus in the 
kidney should invade the kidney -pelvis, there will result a clissemiyiation 
of tubercle-bacilli over the surface of the mucous membranes. From the 
bronchi the bacilli spread into the trachea, larynx, mouth -cavity, and 
thence into the alimentary canal ; through aspiration during deep quick 
inspiration, they may be carried into other portions of the lungs as yet 




Fig. 474.— Tuberculosis of the veins in the neighborhood of a tuberculous r etroperitoneal lymph-gland 
(formalin, hsematoxylin, eosin). a.. Tuberculous lymph-gland with giant-cells and caseous foci; large 
blood-vessels at the periphery ; h, veins w^hose walls are thickened by tuberculous granulation tissue, the 
inner layers of which show caseation ; c, fat tissue. X 38. 

unaffected. From the kidneys the bacilli may be spread throughout the 
descending urinary passages. 

A secondary infection may also result from this spreading of the 
bacilli, yet only a small percentage of the bacilli thus distributed give 
rise to an infection ; and experience has taught us that only certain por- 
tions of the mucous membranes are susceptible to infection — particularly 
33 



626 



THE PATHOGENIC FISSIOX-FUNGI. 





the tonsils and the lymphadenoid tissue of the small and large intestines, 
while the oesophagus and stomach are almost immune; and in the case 
of the descending urinary x^assages, the kidnej'-pelvis, the ureters, and 

bladder are usually infected 
while the urethra almost always 
remains uninvolved. 

If bacilli enter the great 
body=cavities they can also 
spread over the surfaces of the 
serous membranes, infect the 
latter, and excite a diffuse in- 
Hammation and formation of 
nodules (Fig. 476). Anew-for- 
ination of connective tissue may 
follow later. 

Should tubercle- bacilli be 
present in the circulating blood 
of a woman during pregnancy, 
the infection of the placenta 
and foetus may follow, so that 
the child will be born already 
infected. In so far as data con- 
cerning this point exist, this 
event is not of frequent occur- 
rence; and it is more usual for 
children of tiihercnJous pco-ents to 'become infected after birth. A concep- 
tional infection of the embryo through infected semen has not yet been 
demonstrated, and is very unlikely. 

Secondary infections are not infrequently associated with that caused 
bv tubercle-bacilli, and 



Fig. i75.— Heematogenous miliarj- tuberculos 
liver (alcohol, carmine), o. Developed tubercl 
connective tissue about the portal vein*; h, vnUf 
leucocytes. X 1.50. 



s of the 
in the 
•tion nf 



this occurs particularly 
when the disintegration- 
cavities or ulcers are ac- 
cessible from without. 
Secondary in fections of tu- 
berculous lungs are of very 
frequent occurrence, and 
are due particularly to 
streptococci 'and staphylo- 
cocci, pneumococci, influ- 
enza-baciUi, micro coc c u s 
tetragenus, and bacterium 
coli. Many authors are 
inclined to refer all severe 
inflammatory exudations 
accomi^anying ^^ulmonary 
tuberculosis to such secon- 
dary infections; but this 
IS not correct in so far 
that the formation of tu- 
bercles by tubercle -bacilli 
may be accompanied by 
inflammatory exudations 
of such severity that 




Fig. 476.— Tuberculosis omenti (Miiller's fluid, carmine), a. 
Centre of tubercle : h, cells of epithelioid character ; c, lym- 
pbatic elements; d. proliferatino- epitliPlium (endothelium) in 
the neighborhood. A 20r). 



TUBERCULOSIS. 



627 



serous or serofibi'iiious, or ]>nre libi'iiious, or fibrinopiiruleut exudates 
may collect in large quantities in the tissues (in the pulmonary alveoli, 
on the pleura, and in the subarachnoideal space, etc.). A high (septic) 
fever, ]'apid destruction of tissues with a tendency to suppuration, and 
an unusually severe intlamniation, iu part of a htTmorrhagic character, 
point to a secondary infection. ^Nevertheless, it is often impossible to 
determine, without a special investigation directed to this point, whether 
a pure tuberculosis or a mixed infection is present. 

For the treatment of tuberculosis with bacterial extr;icts and curative 
serum see § 32. 

The question as to how often tuberculosis is transmitted by the passage of 
bacilli from the mother to the child is still an open one. It has, however, been 
shown by Schmorl, Birch-Ilirschfeld, and Landouzy that in cases of miliary tuberculosis 
in pregnant women, tubercle -bacilli are present both in the intervillous spaces and in 
the blood of the chorionic vessels, and that the liver of the foetus may contain bacilli. 
Further, cases of tuberculosis of the placenta also occur {Sclimorl, Kockel, Lungwitz), 
which may be regarded as stages on the way of the tubercle-bacillus from the mother 
to the feetus. 

Cases of tuberculosis occurring at an early period of life, repoj-ted by Deiume, 
Baumgarten, RilUet, Charrin, and others, as well as the statements of Armanm, Lnn- 
douzy, and Martin, that the inoculation of portions of the organs of human foetuses 
obtained from tuberculous mothers produced tuberculosis in guinea-pigs, speak in favor 
of a passage of tubercle-bacilli fi'oin the mother to the foetus. Still more important are 
the experimental investigations of de Renzi and Gartner, who succeeded through the in- 
oculation of pregnant guinea-pigs, white mice, and rabbits in producing tuberculosis in 
a part of the young born of these animals. Gartner m consequently of the opinion that 
under certain conditions tubercle- bacilli may pass from the mother to the foetus in the 
case of both animals and man. Finally, Maffucci and Baumgarten succeeded in effecting 
a transfer of tubercle-bacilli to impregnated hen's eggs, and discovered that the infec- 
tion did not disturb the development of the chick, but, on the contrary, the bacilli that 
were taken up by the embryo remained in the tissue of the latter without multiplying 
to any extent, later to cause a tuberculosis in the body of the hatched-out chick. Ac- 
cording to the investigations of Friedmarui t\\herc\(iAya.Q\\\\ deposited at the same time 
with semen, in the vagina of rabbits, gained entrance into the embryo and could still 
be demonstrated on the sixth day. 

The experiments cited above not only justify the assiuuption that bacilli may be 
transferred from the mother through the placenta to the child, but also that they may 
remain iu the body of the embryo for a long time without causing specific changes. 
The occurrence of a conceptional tuberculosis through the transmission of bacilli in the 
semen is still a question. It must be noted, however, that the semen and the contents 
of the seminal vesicles often contain tubercle-bacilli, not only in cases of tuberculosis of 
testicle and epididymis, but also in cases in which no tuberculous affection of the sex- 
ual apparatus could be demonstrated. In general, the following principles may be 
summed up: Tuberculosis is usually to le referred to an extra-uterine infection ; and the 
children of tuberculous parents suffer so frequently from this disease, because the)'" are 
more exposed to infection unth tubercle-bacilli than are the children of healthy individuals. 
A special predisposition of the cliildren of tuberculous parents to tuberculosis has not 
been demonstrated. 

In animals a transmission of tuberculosis to the foetus seems occasionally to occur, 
according to the rej^orts of Zippelius, Jessen, Piitz, Grothans, Malvoz, Lydtin, Broumer, 
Adams, and others. JoJtne was not only able to demonstrate in a foetal calf the pres- 
ence of miliary nodes and larger nodules in the lungs, liver, and various lymph-glands, 
but also to show the presence of characteristic bacilli in the lesions. 

From the side of clinicians and physicians the so-called scrofula has been many 
times regarded as an especial pathological condition of the organism of the child, pre- 
disposing it in an especial degree to tuberculosis. As scrofulous are regarded those 
children who permanently or at least very frequently suffer from inflammations of the 
mucous membranes (nose and its accessory cavities, conjunctiva, middle ear), as well as 
of the skin, also from swelling of the lymph-glands leading occasionally to necrosis and 
suppuration, tinally also from chronic inflammations of the bones and joints, and who 
present a flabby, pale, often bloated appearance. In many cases these symptoms are 
due to tuberculosis; in other cases they are caused by an infection with streptococci or 
staphylococci, or are the results of syphilis. Scrofula is not a disease entity, but is only 
an especial S3Mnptom-complex belonging to different diseases. Whether the affected 



628 



THE PATHOGENIC FISSION- FUNGI. 



children possess an especial predispo.^itlon t'> (ill tJusc i nu rtt'nns Aviiich may be designated 
ix^ scrofula is difficult of proof. The org-anisin of the child is in general easily infected 
by these agents, and the frequent illness of certain children due to these infections may 
be referred to a lack of cleanliness, or to especial conditions of the environment of the 
child, or to frequent injuries, etc., as well as to an especial predisposition of the child 
itself. 

Tuberculosis of mammals is ob.served most frequently in the case of cattle, and 
presents in general a course similar to that of the disease in man. though the granula- 
tion-areas develop more frequently into larger tumor-like nodules, particularl}' so in 
cattle, and the tendency to a generalization of the disease is less. The tuberculosis of 
the serous membranes which is often designated as pearl disease {" 1\ rl-<iic]d ") begins 
with the formation of small nodules, leading then to a more marked proliferation of the 
connective tissue, giving rise to the formation in the thickened sero-a of nodules of the 
size of a pea or bean or even as large as a hen's egg or man's fist (Fig. 477). which in 
the beginning are soft and sarcoma-like, but later become firmer and denser and often 
enclose calcified areas of caseation. The form of the proliferation is sometimes vilhuis- 

like and warty, at other times of 
a mulberry- or grape-like form, 
cauliflower -like or even polypoid. 

Xext to cattle the hog is most 
frequently affected with tubercu- 
losis, more rarely the horse, goat, 
<li(^e]^. cat. and still more rarely 
Tlie d.)g. 

Of mild ii II i iti Ills \\\ captivity, 
The ape. lir)n. tiger, bear, jackal,, 
imnrlier. jaguar, giraff'e, and drom- 
edary easily acquire tubercu- 
losis. Of the small animals used 
for experiment the guinea-pig is 
the most susceptible. After sub- 
cutaneous inocidalions there re- 
sults a ]irogre.-sive tuberculosis 
which kills the animal in from 
about four to eleven weeks. In 
rabbits an inoculation tuberculosis 
ma}' heal. Field iniee and white 
miec are infected with difficulty. 

Tuberculosis is of frequent 
occurrence in birds (chickens, 
pigeons, pheasants, and parrots), 
but ilie bacillus of avian tuber- 
culii<i< is lint identical with that 
nh'ni, Bii II itirjarten. Rcxjer, 
art caused bv the bacillus 




Fig. 477.— Growths from tlie iileiini ui a oiise of bovine tuber- 
culosis rTerlsucht " ). 



Strinis, (r, 
is in o-reat 



of mammalian tuberculosis {Miif w^'n. BrcUi 
and others); the tuberculosis of parrots alone 
of mammalian tuberculosis. 

The cultures of ttibercle-bacilli from man are dry. warty, or scaly and lustreless; 
those of avian tuberculosis moist, wriidvled, and soft, and moreover grow best at 43^ C. 
Doo-s are wholly immune to avian tuberculosis, but not to human tuberculosis. The 
intraperitoneal inocidation of mammalian tuberculosis [Leray) causes in rabbits numer- 
ous caseous foci in the liver and spleen with few giant-cells and scanty bacilli, and in the 
luno-s numerous caseous nodules containing numerous bacilli. Inoculations into these 
animals of chicken-tubt rculo.sis, on the other hand, cause a scanty production of non- 
caseatino- cellular proliferations containing giant-cells and great numbers of bacilli. 

Accordino' to Maffucci, Martin, and Ocfrtncr, the inoculation of human tuVterculosis 
into chickens" does not produce tuberculosis, but the bacilli remain alive for weeks 
^vithin the bodv of the chicken. Pigeons iA' rhi/r) die after intraperitoneal inoculation, 
t)ut no tubercles are found in the tissues: the liver and lungs may contain living bacilli 
fourteen davs after the inoculation. In guinea-pigs (Straus) the bacilli of human 
tuberculosis cause much more severe changes than do the bacilli of chicken-tubercu- 
losis. Whether man is susceptible to avian tubercidosis is still an open question. 

As pseudotuberculosis mav be classed all those affections characterized by the 
formation of cellular and fibrous nodules, and in part also undergoing necrosis, and which 
are similar to tubercles, but which are not caused by Eoch's bacillus. According to 
the etiolo2:v the following forms may be distinguished : 

1. Pseudotuberculosis due to dead foreign bodies. This may be caused by the experi- 
mental injection of lycopodium-spores, olive-oil, and mercury into the blood-vessels. 



TUBERCULOSIS. 



629 



the inhalation of irritating material into the lungs, the injection of large quantities of 
milk into the peritoneal cavity, etc. The presence in the tissue of caterpillar hairs, 
pieces of wadding, silk threads, etc.. cholesterin tablets from ruptured ovarian cysts, 
and .stomach-contents which have gained entrance into the peritoneal cavity, etc.. may 
also lead to the formation of tibrocellnlar nodules. 

2. Pseudot'iht rc^doxi>< canscl hi/ inniniinnrphniis and imlijuKiriiliniis l„h-i, rl,i . I-^.fiiii n'j< i\ 
Bucholz. and Flexner have described forms of (_'hid,,thrix and St rrjitntj, ri.r obtained from 
apparently tuberculous lungs and bronchial glands which they are inclined to regard 
as the cause of the disease. Courmont found in an apparently tuberculous elbow-joint 
a bacillus which was not identical with AV//".v bacillus. An affection of the peritoneum 
resembling tuberculosis may be produced in guinea-pigs by the injection of the 1)ntter- 
bacillus oi Eabinniritf<ch{\\]i\Q\\ probably comes from cow-dung) as well as by the grass- 
bacillus of Moeller; and in white mice by the inoculation of the butter-baeilkis of lv<.ni. 

In the rodents a disease resembling tuberculosis is not infrequently produced by a 
plumi>. thick bacillus with rounded ends {Pjeijfer. Prcisz. Zagnri. y>>r</,yJ. Bnn, ,,,,(. Dd- 
hanco. and others). Other forms of bacillary pseudotuberculosis have Ijeeu observed in 
rabbits {FJh rfli). in birds (Mnir), in the cow {C»n ripont). etc. 

3. P.sY udntiilu rrulosis d'K: to liyphomycetes occuis in the lungs and may be produced 
artiticially by the injection of different forms of aspergillus and mucor: but the affec- 
tions so produced sliow pecidiarities which make possible a differentiation from true 
tuberculosis. 

4. Psendnt nh, rcidnsis mused hi/ (ininnd jhi riis!t,_s occurs particularly in the sheep, 
hog, goat. cat. hare. roe. stag, and chamois, and is caused by different i'orms of Stroa- 
gylus and by Pseudalius riipiibrris {Miiller); it is therefore a vermian pseudotuberculosis. 



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d'Arrig-o; Uebertragung der Tuberk. durch die Placenta. Cbl. f. Bakt., xxvii.. 1900. 
Barie: Rech. zur la tuberculose senile. Rev. denied.. 1895. 

Baumgarten : Samml. klin. Yortrage v. Volkmann, Ijeiliner klin. Woch., 

1888; Experimentelle congen. Tuberkidose. Arl). a. d. path. Inst, zu Tubingen, 
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Benda: Acute ^liliartuberkulose. Berl. klin. Woch.. 1899. 

Brehmer: Die Aetiologie der chron. Lungensehwindsucht. Berlin, 1885. 

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Cohnheim : Die Tuberkulose vom Standpunkt der Infectionskrankheiten. 1880. 

Cornil et Leloir: Lupus. Arch, de pliys.. iii.. 1884. 

Demme: Bacillen in luposen Herden. Berl. klin. AVoch., 1893: Ueber tuberkulose 

Ekzeme. xx., xxi. Jahiesber. d. .Tennerschen Kinderspitals, Bern. 1883, 1884. 
Dennig-: Tuberkulose im Kindesalter. Leipzig. 1896. 
Doutrelepont : Lupus u. Miliartul)erkulose. Deut. med. "\Yoch.. 1885. 
Diirck: Tuberkulose. Ergebn. d. allg. Path., ii.. Wiesbaden, 1897 (Lit.). 
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Fraenkel u. Troje: Pneumomsche Form d. Luno-entuberkulose. Zeitschr. f. klin. 
3Ied.. xxiv., b^93. 

Friedlander: Loc. Tub. Klin. Vortr. v. Volkmann, Xo. 64; Lupus. Yirch. Arch., 
60 Bd.. 1874. 

Friedmann: Gaumentonsille als Eiugangspforte. Beitr. v. Ziegler, xxviii., 1900; 

Studien liber die Erblichkeit der Tuberkulose. Deut. med. Woch., 1901. 
Garre; Aetiologie der kalten Abscesse. Deut. med. Woch.. 1886. 
Gartner; Ueber die Erblichkeit der Tuberkulose. Zeitschr. f. Hyg., xiii., 1893. 
Gatti; Sul proc. di repress, della peritonite tub. per la laparotomia. Arch, per le Sc. 

Med.. xxi.. 1897 (Lit.). 
Hahn: Tuberculose congen. et hered. Rev. de la tub.. 1895. 

Hauser: Die Yererbung^der Tuberkulose. Deut. Arch. f. klin. Med.. 61 Bd.. 1898. 
Henke: Intra-uterine Infection. Arb. her. v. Baumgarten. ii., 1897. 
Hering: Studien liber Tul)erkulose. Berlin, 1873. 

Jakowski; Mischinl'eetionen d. Phihisiker. Cbl. f. Bakt.. xiv.. 1893. 
Jackh; Bacillenii-ehalt d. Geschlechtsdriisen Tuberkuloser. Yirch. Arch., 142 Bd., 
1895. 

Johne; Geschichte d. Tuberkulose. Leipzio-. 1883: Congen. Tub. Fortschr. d. Med., 
iii., 1885. 

Jousset; Transmission de la tuberculose. Et. sur la tub. publ. par Yerneuil. iii., 1892. 



630 



THE PATHOGENIC FISSION- FUNGI. 



Kockel u. Lung-witz: Placentartuberkiilose beini Umd. Bvitv. v. Ziegier, x\ i , 1S94. 

V. Koranyi: LiingensclivviiKlsiiclit. Eulenburg's Healeneyklop. . 1897. 

Kossel: Tuberkulose im friiben Kindesaltei'. Zeitsehr. f. Hyg., xxi., 1895. 

Konig: Die Tuberkulose der Kuochen und Gelenke, 15erliii, is84. 

Kiittner: Lupus d. Finger u. Zehen. Beitr. v. Bruns, xviii., 1897 (Lit.). 

Iiandouzy: Heredite tubereuleuse. Rev. de med., xi., 1891. 

Lang-erhans: Zur Aetiologie der Phtbise. Vircb. Ardi., 97 Bd., 1884. 

Lartigau: Cbronic Hyperplastic Tuberculosis of tbe Intestine. Studies from Dept. 

of Patb. of Columbia University, 1901-2. 
Maffucci: Sulla infezione tubercolare deuli embrioni di polio. Ref. Cbl. f. Bakt., v., 

1889. 

Malvoz et Brouvier: Deux cas de tuberculose coniien. Ann. de I'lnst. Pasteur, iii.. 
1889. 

Meyer: Aussclieidungstuberkulose d. Nieren. Yircb. Arch., 141 Bd., 1895. 
Mogling-: Ueberchir. Tuberkulos. Mittbeil. a. d. cbir. Klinik v. Bruns, i., Tlibingeu, 
1884. 

Ortner: Die Lungentuberkulose als Miscbinfection, Leipzig, 1893. 
Pasquale: Die Streptokokken bei der Tuberkelinfection. Cbl. f. Bakt., xvi., 1894. 
Petruscliky; Tuberkulose u. Septikamie. Deut. med. Wocb., 1893. 
Predohl: Die Geschiclite der Tuberkulose, Hamburg, 1888. 
Ribbert: Ueber die Ausbreitung der Tuberkulose im Korper, i\Iarburg, 1900. 
Sanchez-Toledo: Transmission de la tubercul. de la mere au foetus. Arch, de med. 
exp., i., 1889. 

Sata: Die Bedeutung d. Miscbinfection bei Lungenscbwindsucbt. Beitr. v. Ziegier 
Suppl., 1899. 

Schlenker: Menscbl. Tuberkulose (Statistik). Vircli. Arch., 134 Bd., 1893. 
Schmorl u. Birch-Hirschfeld : Uebergang von Tuberkelbacillen aus dem miitter- 

lichen Blut auf die Frucbt. Beitr. v. Ziegier, ix., 1891. 
Schmorl u. Kockel: Tuberkulose der menscbl. Placenta. Beitr. v. Ziegier, xvi., 1894. 
Schottlander : Ueber Eierstockstuberkulose, Jena, 1897. 
Schiippel: L'nters. iiber Lj^mpbdrlisentuberkulose, Tubingen, 1871. 
Schurhoff: Patbogenese der allgem. Miliartuberkulose. Cbl. f. allg. Path., iv., 1898. 
See, G. : La pbtliise bacillaire, Paris, 1884 
Straus: La tuberculose et son bacille, Paris, 1895. 

Verneuil : Etudes sur la tuberculose, Paris, 1887-93 ; Rev. de la tub. , 1893-99. 

Virchow: Die krankbaften Geschwlilste, ii.. Berlin, 1865. 

Wagner: Das tuberkelabnlicbe Lympbadenom, Leipzig, 1871. 

Weigert: Die Entstelumg d. acuten Miliartuberkulose. Deut. med. Wocb., 1897. 

Wild: Entstebung der Miliartuberkulose. Yircb. Arcb., 149 Bd., 1897. 

Ziegier: Ueber Tuberkulose u. Schwindsuclit. Samm. klin. Vortr. v. Volkmann, No. 

151, 1878; Tuberkulose. Eulenburu's Realencyklop., xxiv., 1900 (L''t.). 

See also § 166. 



(Tuberculosis of AnhnaJs. Psendotuhercidosis. ) 

Apostopulos: Histologic d. Pseudotuberkulose. Arb. ber. v. Baumgarten, ii., 1896. 
Auclair: La tub. liumaine cbez le pigeon. Arcb. de med. exp., 1897. 
Bang: Eutertuberkulose u. tuberkulose Milcb. Deut. Zeitsclir. f. Tbiermed., xi., 1885. 
Baumgarten: Uebertragung d. Tuberkulose durcb die Nabrung. Cbl. f. klin. Med., 
1884. 

Bollinger: Ideutitat d. Perlsucbt mit menscbl. Tuberkulose. Miincb. med. Wocb., 
1895. 

Bonome: Sulla pseudotuberculosi microbica. Arcb. per. le Sc. Med., xxi., 1897 (Lit.). 
Chantemesse : La tuberculose zoogleique. Ann. de I'lnst. Pasteur, 1887. 
Courmont: Tuberc. bacillaire d'origine bovine. Et. sur la tub. publ. par Yerneuil, ii., 
1890. 

Delbanco: Pseudotuberkulose d. Nagetbiere. Beitr. v. Ziegier, xx., 1896 (Lit.). 
Eberth: Pseudotuberkulose d. Kanincbens. Fortscbr. d. Med., 1885; Yircb. Arcb., 
102 Bd., 1885. 

Frothingham: Impfversucbe an Kiilbern. Zeitscbr. f. Tbiermed., i., Jena, 1897, 
Gadiot, Gilbert et Roger: Inocul. aux gallinaces de la tuberculose des mammiferes. 

Mem. de la Soc. de biol., 1891. 
Gilbert et Roger: Inocul. de la tuberculose aviaire au cobave. Mem. de la Soc. de 

biol., 1891. 

Grancher et Ledoux-Lebard: Tuberculose zoogleique. Arcb. de med. exp.. 1889, 
1890. 



SYPHILIS. 



631 



Jeanmaire. Hist. Veraud. bei d. verminosen Pueumonie d. Katzeii ii. Hasen. Inaug.- 
Diss., Freiburg, 1900. 

Jensen: Tuberkulose beim Himd und bei der Katze. Dent. Zeitscli. f. Thiermed., xvii., 
1891. 

Johne: Die Gescliichte der Tuberkulose, Leipzig, 1893; lliilmertuberkulose. Deut. 
Zeitsclir. f. Thiermed. ^ x. ; Uebertragung der Tuberkulose v. Menscli auf Hund. 
lb., xiv., 1889. 

Kastner: Infectiositat des Fleisches perlsiichtiger Tliiere. Miincli. med. Wocli., 1892. 
Kostenitsch. et Wolkow: Tuberculose aviaire cliez le lapin. Arch, de med. exp., 
v., 1893. 

Kruse: lluhnertuberkulosebeim Mensclien u. Saugethier. Beitr. v. Ziegler, xii., 1893. 

Leray : Tub. de I'homme et tub. aviaire. Arch, de med. exp., vii., 1895. 

Maffucci: Aetiologie d. Tub. Cbl. f. a. Path., i., 1890; Hiihnertuberkulose. Zeitsch. 

f. Flyg., xi., 1892. 
Mair: On Pseudotuberculosis. Journ. of Path., v., 1898. 
Malassez et Vignal: Tuberculose zoogleique. Arch, de phys., iv. , 1884. 
Miiller: Die JSTematoden d. Saugethierlungen. Deut. Zeitschr. f. Thiermed., i v., 1889. 
Pfeiffer, A. : Ueber die bacillare Pseudotuberkulose bei Nagethieren, Leipzig, 1888. 
Piitz: Ueber die Bezieh. d. Tuberkulose des Mensclien zur Tub. d. Thiere, Stuttgart, 

1883. 

Ribbert: Verbreitung der Bacillen bei Huhnern. Deut. med. Woch., 1883. 
Straus et Gamaleia: Rech. exp. sur la tuberculose. Arch, de med. exp., iii., 1891. 
Wehmer: Perlsucht. Eulenburg's Realencyklop., xviii. , 1898 (Lit.). 
Zagari: Tuberculosis zoogloeica oder Pseudotuberkulose. Fortschr. d. Med., vii., 
1890. 

Zieg-ler; Tuberkulose. Eulenburg's Realencyklop., xxiv., 1900 (Lit.). 
See also § 166. 

§ 168. Syphilis is, like tuberculosis, an infectious disease, which, 
proceeding from a local infection, spreads throughout the organism by 
means of the blood- and lymph-channels, and leads to the formation of 
localized inflammations and proliferations of granulation tissue, which, 
however, do not present so characteristic a structure as does the tubercle. 

As the cause of syphilis there was described by Lustgarten, in 1884, 
a bacillus which, it is possible, may have pathogenic significance and 
may represent the contagium of sypliilis. The only point in favor of this 
assumption is the fact that the bacilli have been demonstrated in all 
stages of the most varied forms of S3'i)hilitic foci. The bacilli have not 
yet been cultivated. 

The bacillus is similar to the tubercle bacillus, 3 to 7 ii long, often 
curved, and somewhat swollen at the ends. According to Lustgarten it 
may be made visible by a complicated staining-process, by which the 
sections are stained in aniline-gentian-violet solution, then decolorized 
in potassium permanganate, and washed in sulphurous acid. Other 
authors have more recently published other methods. 

The bacilli are found in syphilitic foci only in small numbers, and lie 
for the greater part from one to four in a single cell (Lustgarten), but 
also between the cells, and are at times also present in the blood (Dou- 
trelepont). The Lustgarten bacillus can hardly be used, at the present 
time, as an aid to differential diagnosis, since the smegma-hacillus found 
in the preputial secretion and in the smegma between the labia majora 
and the labia minora stains also by the method described by Lustgarten. 
According to Doutrelepont, Klemperer, and Lewy, it is possible to dis- 
tinguish these bacilli from one another by proper staining methods (car- 
bol fuchsin). 

The poison through whose inoculation syphilis is produced occurs 
only within the human organism, Avhere it is alone reproduced ; and is 
communicated to other individuals only by direct or indirect transfer. 
When implanted in an organism it excites inflammatory processes of 



632 



THE PATHOGENIC FISSION- FUNGI. 



the most varied intensity and extent — from a simple local transitory 
liyper^emia to the production of large exudates or tumor-like granula- 
tions, or extensive hyperplasias of connective tissue. If a child is be- 




FiG. 478.— Initial sclerosis (alcohol, htematoxylin. eosin). a, Corlum, slightly inflamed; b, initial 
sclerosis : connective tissue infiltrated with cells ; c, rupttire of the cells into the epithelium ; d, e, lymph- 
vessels filled with leucocjles. X 85. 




gotten in the presence of a syj)hilitic infection, the disease may be trans- 
mitted to the foetus hj the father as well as by the mother. 

If the first focus of inflammation develops at the point of infection, 
which is usually located in the skin or mucous membranes (mouth, 
throat, mucosa of genital apparatus), there is formed first a papule 
which spreads toward the surface, and Avithin eight to ten days after its 
appearance forms scales, or ulcerates and secretes a small amount of 

serous or purulent fluid which dries 
to a scab ; at the same time its base 
W)/ hecomes hardened and forms a 
thick disc-like or a thin parchment- 
like deposit in the skin. Occasion- 
f ally a vesicle is also formed, and 
^ this becomes an erosion, and then 
■W'^ an ulcer with scanty secretion and 
xC% having an indurated base. In 

still other cases an ulcer is first 
formed, and the base becomes in- 
durated subsequently. 

The induration is called the in= 



'^K"^^^^"^ "^^^ itial sclerosis or the Hunterian in- 

FiCr. 479.-Section from a s:.T)hilitic initial sclero- duration (Fig. •47*'^. h ) ', the ulccr iS 
sis (alcohol, alum caniiiiie^. a. Round-cell infiltra- ti-,nwri q« q hnnl nhnnovp TliP 
tion: 7x laree UK. nMtiuripar formative cells ; c. mul- KUOA^ n aS d /laid C/UUlCte. ±nt^ 

tinuciear formative cells. X 350. formcr is causcd esscntially by a 

collection of small round ceJl-s (Figs. 
478. I) : 479, a) in the si^aces of the connective tissue. Occasionally 
epithelioid cells (Fig. -479, b) and isolated giant-cells are also formed ( r). 




SYPHILIS. 



633 



With these changes the height of the process is reached ; the greater part 
of the tissue disintegrates and ulcerates, or is absorbed after disintegra- 
tion. A part of the cells are utilized in the formation of scar tissue. 

Within the area of the initial sclerosis and its immediate neighbor- 
hood the lymph -vessels (Fig. 478, d, e) are dilated and filled with leuco- 
cytes. Later, after the lapse of a certain length of time the lymph- 
glands, the skin, and the mucous membranes become involved in 
inflammatory processes (symptoms of the secondary stage). Still later, 
there follow syphilitic inflammations of the internal organs and the bones 
(tertiary stage). These are in part like other non-syphilitic inflamma- 
tions, but special forms of granulation tissue are sometimes produced. 
The syphilitic affections of the skin which are grouped under the term 
syphilides form sometimes only red si^ots, sometimes larger or smaller 
papillary elevations which may be associated with the formation of vesi- 
cles and pustules as well as with the production of scales. Accordingly, 




Fig. 481).— Condyloma latum ani (alcohol, Bismarck-brown), a, Horny layer; 7), mucous layer of the 
epidermis; c, corium; d, loosened horny layer infiltrated with small cells; e, swollen, /, swollen and in- 
filtrated mucous layer; o, epithelial cells containing round cells; lu granular masses of coagula; i, swollen 
papillary body infiltrated with cells and fluid ; /.-, corium, swollen, and infiltrated with cells, fiuid and coag- 
ulated albumin ; /, dilated lymph-vessels filled with clots; w, sweat-glands. X 150. 

the different forms of cutaneous syphilides have been called by different 
names, as follows: Roseola sypMUtica, and papular, vesicular, pustular, 
and ulcerative syphilides, as well as a psoriasis syphilitica (cf. Pathological 
Anatomy of the Skin). A common element in all these affections is a 
more or less marked inflammation, which is characterized particularly 
by a tissue-infiltration and in part also by proliferation. Thus, for ex- 
ample, in the large papular syphilide or condyloma latum there is a beet-like 
elevation of the skin caused by an infiltration of the papillary body (Fig. 



6U 



THE PATHOGENIC FISSION-FUXGI. 



480, i), the corinm (A- 1, and also tlie epithelium {e,f. g, h j ^vith cells and 
a fluid exudate which coagulates with the hardening of the tissue. If the 
horny layer of the epidermis becomes macerated, these masses of exudate 
may appear upon the surface, and give rise to a moist condition of the 
condyloma. In the pustular syphilides the inflammation leads to a puru- 




FlG. 481.— Meninaro-encephalitis syphilitica gummosa (Miiller's fluid, alum carmine ). a. Brain cortex; 
inner meninges; c. vein surrounded bv cellular exudate ; fresh cellular granulation tissue; dj. Qbro- 
cellular granulatiun tissue; f'n.caseated <rranulation tissue; r. artery with markedly thickened intima and 
adventitia infiltrated with cells; r. cellular inrlltration of the pia-sheaths of the cortical vessels; /i. peri- 
vascular cellular infiltration of the cortical substauce ; g. dlffuselv spreading: cellular infiltration invading 
the brain-substance. ■: U. 

lent licjuefaction of the epithelium, and in the ulcerating forms also of 
the papillary body and of the corimn, so that uJcejs result. 

Inflammatory changes similar to those in the skin appear, in the sec- 
ondary stage of syphilis, also in the mucous membranes, particularly of 
the mouth, throat, and respiratory passages. 

The syphilitic lesions of the tertiary stage, appearing in the inter- 
nal organs, in the glands, bones, muscles, subcutaneous and submucosal 
tissues, in the meninges of the brain, etc., in so far as they consist not only 
of slight degenerativ e and inflammatory processes or hyperplasias of cou- 
nective tissue without characteristic features, appear as formations which 
are usually designated as gummata f Virchow ). In its early stages the 
gumma, as well as the broad condyloma, represents an inflammatory 
process localized to one tissue-area ; but the gumma is usually more rich 
in cells and not infrequently attains a higher degree of development in 
so far that a i)eculiar form of granulation tissue with new vessels ( Fig. 
-4S1, d, d^ ) is formed. The gumma occurs particularly in the ijeriosteum 
and membranes of the brain, as well as in the parenchymatous organs of 
the abdomen, especially in the liver, spleen, and in the testicles: and 
shows a difi'erence in the abundance of its cells according to location. 
The forms which are i^oor in cells are observed chiefly in the bones ; they 
are soft in consistence and on section present a gelatinous appearance, 
in that the fluid portion of the node is in excess of the cellular mass. 
The tissue also undergoes a partial metamorphosis into mucous tissue. 



SYPHILIS. 



635 



The gummata rich in cells are found especially in the inner meninges 
(Fig. 481), in the snbniucosa of different mncons membranes, in the 
skin, liver, testicles, and spleen ; and form gray, or grayish- white or 
grayish -red, sometimes spherical (spleen, testicles), at 'other times more 
irregnlarly sha^jed, nodnles (inner meninges), whicli in their light-gray 
or reddish-gray color and some^yhat translncent character are similar 
to normal granuJation tissue. Besides these lesions, diffnse inflammatory 
changes are often present in the affected organs. 

Small syphilitic foci of iiifiltration often vanish qnickly throngh 
absorption ; in larger ones there occnrs frequently a snpj)nration or a 
fatty and necrotic disintegration. The disintegration of syi)hilitic foci 
of the skin and subcutaneous tissue, as well as of the mucosa and snb- 
niucosa, leads to the formation of ulcers, which, in the case of the mucous 
membranes, occur most frequently in the region of the mouth, throat, 
and the upper respiratory tract (Fig. 483, a). In the interior of deeper- 
lying gummata there are not infrequently formed caseous areas (Figs. 
481, d.,] 482, a), Avhich are at times regularl}^ spherical, at other times 
irregularly shai^ed. The peripheral portions pass over into a scar-like 
connective tissue (Fig. 482, b, c, d) which encloses the caseous areas and 
radiates in bands into the surrounding tissues. In the neighborhood of 




Fjg. 482.— Gumma hepatis (alcohol, alum carmine), a, Caseous nodule; &, homogeneous connective 
tissue; c, connective tissue with remains of liver tissue; d, connective-tissue bands radiating into the 
liver tissue ; c, cellular focus at the edge of the caseous nodule ; f, cellular focus within the connective- 
tissue rays ; (/, liver tissue. X 13. 

the ulcers arising in mucous membranes there are not infrequently formed 
papillarij prolifemtions (Fig. 483, 6, c). 

Necrotic remains of gummata which originally were cellular come 
under anatomical examination far more frequently than those which are 
still x^erfect, and in this condition are usually still designated as gum- 
mata. I^ot only does the cellular new-formation take part in the devel- 



636 



THE PATHOGENIC FISSION- FUNGI. 



opmeut of the gumma, but also the inJiUrated tissue itself, in that the 
latter also undergoes neerosis aud becomes caseated. 

The cause of the frequeut disiutegratiou aud uecrosis occurring in 
syphilitic iutlammatious lies in the peculiar character of the exciting 
cause of the disease. A second factor may also be largely responsible 
for this manner of termination — namely, the extensive participation of 
the blood-vessels, particularly of the arteries, iu the inflammation. 
When a syphilitic intiammation leads to the formation of granulation 
tissue or to a connective -tissue hyperplasia, the vessel- walls also become 
thickened, particularly the intima (Fig. 481, e), so that the vessel-lumen 
is narrowed and not infrequently completely closed. Occasionally the 

syphilitic process is localized chiefly in 
the vessels. 

Besides the peculiar foci of inflam- 
mation which point to a localization of 
the exciting cause of syphilis, there not 
infrequently occur in individuals who 
have suffered a syphilitic infection 
sipGciiiG degenerations of the central nervous 
system (tabes, progressive paralysis), 
which are associated with proliferations 
of neuroglia, ^^^evertheless, these affec- 
tions, though regarded as the sequela' of 
si/j)hiJis, present histologically no peculi- 
arities characteristic of syphilis, and 
'itf occur iu the same form iu other individ- 

f' uals who have never had a svphilitic in- 

11^ I fectiou. 

Hereditary syphilis is characterized 
chiefly by peculiar tissue-changes, which 
differ considerably from the manifesta- 
tions of acqnired syphilis, but changes 
also occur which correspond to the latter. 
In the skin hereditary syphilis may cause 
macular, papular, aud pustular syphil - 
ides which may lead to ulceration. The 
spleen is usually more or less enlarged, 
and in individual cases may attain ten 
times its normal volume. In the liver 
there occur intravascular and perivas- 
cular collections of round cells which 
often collect in small closely packed foci ; associated with these there 
is a periportal new-formation of connective tissue. There is also a 
diffuse hyperplasia of connective tissue throughout the entire liver 
(Fig. 484, a, h), giving to the organ a firm consistence and a peculiar 
yellowish-brown color. Further, there is also a proliferation of connec- 
tive tissue limited to the periportal tissue. The lungs may present, 
throughout or in part, a dense gray or grayish-white structure resem- 
bling that of sarcoma tissue. This appearance is due to the formation 
in the altered area of a cellular connective tissue (Fig. 485, a, b) which 
contains only imperfectly developed alveoli (e, ej and bronchi (d, dj 
or none at all. In cases of slight severity there exists only a thick- 
ening of the peribronchial and peri\'ascular tissue and interah eolar 
septa, in part associated with an accumulation of desquamated epithe- 




FiG. 483.— Sypliililie ulceration of tlie 
larynx. Sagittal section throuarh tbe larynx 
and trachea, a. Ulcer ; b, thickenings and 
papillary proliferations on the epiglottis ; c, 
thickenings and papillary proliferations on 
the left wall of the larynx and the supe- 
rior thyro-arytenoid ligament. Natural size. 



SYPHILIS. 



63T 



lium in the alveoli. In the kidneys and testicles the supporting connec- 
tive tissue may likewise be increased in places, and abnormally rich in 
cells. Syphilis also often causes in glandular organs a pathological develop - 




Fig. 484.— Induration of the liver in congenital syphilis (Miiller's fluid, hgematoxylin, eosin). a, Hy- 
pertrophic periportal connective tissue ; b, indurated gland tissue inflltrated -with connective tissue ; c, 
collections of cells. X 100. 

ment of the connective-tissue elements and collections of cells, while the epi- 
thelial tissues are retarded in their development. In the blood the 
number of white corpuscles appears often to be increased. Finally, 




Fig. 485.— Changes in the lung in congenital syphilis (Miiller's fluid, ha^matoxylin, eosin ) . a, Prolifer- 
ating stroma rich in cells; b, cellular granulation-foci; c\ artery with thickened adventitia ; c7, dj gland- 
like bronchi, which in part (di) contain desquamated epithelium and round cells; e, ej, alveoli, which in 
part (ei) contain desquamated epithelium and round cells. X .52. 



there not infrequently occur in the bones disturbances of endochondral 
ossification, which are characterized chiefly by irregularity in the forma- 
tion of the medullary cavity and in the deposit of lime -salts in the car- 



638 



THE PATHOGENIC FISSION-FUNGI. 



tilage, and lead to disturbances in the structure of the subchondral 
spongy bone-substance. Through the formation of granulation -tissue 
proliferations which undergo caseous necrosis, larger defects may arise 
in the bone substance. 

Syphilis can be transmitted to the foetus by the sperm as well as by the ovum. 
Paternal transmission is more common. After conception a transmission of sj^philis 
from the mother to the f CBtus may take place. The transmission occurs most frequenth- 
in the second stage of syphilis. If infection and conception take place at the same time, 
the disease appears in the child in its most severe form ; but even freshly infected par- 
ents may produce healthy children {Keumann). Syphilis transmitted by the mother 
during the earlj^ months of pregnancy kills the foetus. In the later months of preg- 
nancy sj'philis is as a rule not transferred to the child {JSeumann). 

Healthy women impregnated by syphilitic men may bear syphilitic children, but 
remain free themselves from syphilis throughout their lives. Women who are preg- 
nant with a syphilitic foetus infected from the father, but who have themselves escaped 
contact-infection, acquire through such a pregnancy a certain, though very variable, 
degree of immunity {Hoclisinger). The immunit}' of the mother is the result of the pas- 
sage of immunizing substances to the mother from the foetus infected through the sperm, 
and is therefore not an absolute immunity' {Hoclisinger). 

Hi'igel and Holzhauser affirm that syphilis can be transmitted to swine. 



Literature. 

(Syphilis.) 

Alvarez et Tavel: Rech. sur les bacilles de Lustgarten. Arch, de phys., vi., 1885. 
Baerensprung : Die hereditare Syphilis, Berlin, 1864. 

Bender: Zusammenfassender Bericht liber die Bacillen d. Syphilis. Cbl. f. Bakt., 1887. 
Bitter : Syphilis- und Smegmabacillen. Yirch. Arch. , 106 Bd. , 1886. 
Campana : Dei morbi sifilitici e venerei, Genova, 1889. 

Chotzen: Streptokokken bei hered. Syph. Yierteljahrsschr. f. Derm., xiv., 1887. 
Dohrn: Zur Frage der hereditaren Syphilis. Deut. med. Woch., 1892. 
Doutrelepont : Syphilis u. Smegmabacillen. Yierteljahrsschr. f. Derm., xiv., 1887; 

Streptokokken u. Bacillen bei hei-editarer Syphilis. Centrbl. f. Bakt., ii., 1887. 
V. Diiring: Hereditare Syphilis. Eulenburg's Realencyklop., 1895 (Lit.). 
Eichhorst: Elephantiasis S3-philitica der Lippen. Yirch. Arch., ISl Bd., 1893. 
Finger: Die Syphilis als Infectionskrankheit vom Standpunkte der modernen Bakte- 

riologie. Arch. f. Derm., xxii., 1890; Die Syphilis u. die venerischen Krankheiten, 

Wien, 1901; Die Yererbung der Svphilis, Wien, 1898 (Lit.). 
Fleiner: Ueber Syphilis occulta. Deut. Med. f. klin. Med., 48 Bd., 1891. 
Fournier: Die Yererbung der Syphilis, Wien, 1894; Syphilis hereditaria tarda, Wien, 

1894. 

Hecker: Beitr. z. Hist. u. Path. d. congen. Syphilis, Naumburg, 1898. 

Heller: Die Lungenerkrankung bei angeb. Syphilis. Deut. Arch. f. klin. Med., 1887. 

Hoehsinger: Studien liber die hereditare S3'philis, i., Wien, 1898 (Lit.). 

Hiigel u. Holzhauser: Sypliilisimpfungen am Thier. Arch. f. Derm., 50 Bd., 1900. 

Hutinel et Hudelo: Et. sur les lesions sypliilitiques du foie chez les foetus et les nou- 

veaunes. x\rch. de med. exp., 1890. 
Kassowitz u. Hoehsinger : Ueber einen Mikroorganismus in den Geweben hereditar 

svphilitischer Kinder. Wien. med. Blatter, 1886. 
Lang: Yorl. lib. Pathol, u. Ther. d. Svphilis, Wiesbaden, 1896. 
Lang u. Ullmann: Syphilis. Ergebn. d. allg. Path., v., 1900 (Lit.). 
Lewy: Ueber Svphilis'- u. Smegmabacillen. Inaug. -Diss., Bonn, 1888. Kef. Cbl. f. 

Bakt., v., 1889. 

Lustgarten: Syphilisbacillen. AYien. med. Woch., 1884; Die Syphilisbacillen, Wien., 
1885. 

Mracek: Atlas der Syphilis, Miinchen, 1898. 

Markuse: Stand der Syphilis- u. Smegmabacillen. Yierteljahrsschr. f. Derm., xv., 
1888. 

Matterstock: Syphilisbacillen. Sitz herd. Phys. -med. Ges. zu Wurzburg, 1885; 
L^eber Bacillen bei Syphilis. Mitth. a. d. med. Klinik zu Wurzburg, ii., Wies- 
baden, 1886. 

Mauriac : Lecons sur les maladies veneriennes, Paris, 1890. 



LEPROSY. 



639 



Meyer: Syphilis d. Centralnervensystems. Cbl. f. allg. Path., ix., 1898 (Lit.). 
Miinclieinier : Die extragenitale Syphilis. Arch. f. Derm., 40 Bd., 1897 (Lit.). 
Neumann.: Die Vererbung der Syphilis. Arch. f. Derm., xxiv., 1893. 
V. Niessen: Beitr. zur Syphilisforschung, Wiesbaden, 1900. 
Prockscb.: Die Literatur liber die venerischen Krankheiten, Bonn, 1889-91. 
Rumpf : Die syphilitischen Erkrankimgen des Nervensystems, Wiesbaden, 1887. 
Stroebe: Zur Histologic d. congen. Nieren- u. Limgensyphilis. Cbl. f. allg. Path., ii., 
1891. 

Surico: La Sifilide congenita. Giorn. Ital. della Mai., Ven., 1900. 

Virchow : Die krankhaften Geschwulste, ii. 

Zeissl: Syphilis. Eulenburg's Realeucyklop., xxiii., 1900. 



§ 169. The Bacillus leprae (described by ^^"eisser in 1879 and 1881, 
and by Armaner Hansen in 1880) is a small slender bacillus, from 4 to 6 
long. It is regarded as the cause of leprosy — also called elephantiasis 
Grcecorum. It is found constantly and in great numbers in the diseased 
tissues (Figs. 486, 487, 488). 

The foci of disease in leprosy are in general characterized by a pro- 
liferation (Fig. 486) which consists of cells of different sizes and of a 
fibrous ground tissue. The bacilli lie sometimes between (e), sometimes 
in the cells {c, d), and in the latter appear usually in such great numbers 
that the cells may become greatly swollen (^d) and in part become 
changed into mono- and multinuclear giant-cells (Fig. 487). The latter 
occasionally enclose large vacuoles which contain great numbers of bacilli 
as well as the granular, thready detritus of the liquefied protoplasm. 
The nuclei remain preserved for a long time, and are pressed to the pe- 






FIG. 487. 

Fig. 486.— Tissue from a leprous nodule (alcohol, f uchsln, methylene-blue). a, Flbrocellular tissue ; 
h, round-cells ; c, medium-sized cells ; d, very large cells filled with bacilli ; e, free bacilli. X 200. 

Fig. 487.— Giant-cells, with vacuoles containing bacilli, from leprous proliferations of the nasal mucosa 
(alcohol, Gabbet's stain). X 400. 



riphery by the vacuoles containing the bacilli. Later they are destroyed, 
so that the entire cell becomes changed into a vacuole containing bacilli 
(Fig. 486, d). The cells in which the bacilli lie are in part the original 
cells of the tissue, and in part newly formed cells. 

The bacilli are surrounded by a slimy envelope (E^eisser), and react 
to stains in much the same manner as do tubercle-bacilli. The same 
staining methods may therefore be used for the former as for the latter. 
The stained bacilli often show clear spots or appear as if made up of 
stained granules. 

According to Bordoni-Uffreduzzi the bacilli may be cultivated upon 
peptone -glycerin- blood-serum, upon gelatinized blood-serum, and upon 
boiled eggs. Upon these media they form threads of four times their 
original length, which are often swollen into a club shape at the ends. 
Czaplewski cultivated bacilli, showing a moderate acid-resisting power, 



640 



THE PATHOGENIC FISSION-FUNGI. 



obtained from the nasal secretions of a leprous individual, upon sheep 's- 
blood-serum with the addition of six i^er cent, glycerin. The pure 
cultures thus obtained were then cultivated ui)on v arious ordinary nu- 
trient media. He regards this bacillus as identical with the one cul- 
tivated by Bordoni-Uffredazzi from the bone-marrow of a case of lep- 
rosy. Finally Teich reports observations concerning the successful cul- 
ture of lepra-bacilli. Babes, who also cultivated lepra -bacilli, regards 
them as closely related to the diphtheria-bacillus. Whether the bacilli 
form spores is still a disputed point. 

Inoculations of animals have up to the present time not given positive 
results. It is said that in rabbits an increase of the bacilli and a tissue - 
proliferation may take place at the point of inoculation (Damsch, Tos 




Fig. 488.— Section through a leprous nodule of the stin (alcohol, Gabbet's method), a. Epidermis; 
corium ; c, hair-follicle; cl, leprous focus in the neighborhood of the hair-follicle; e, duct of sweat-gland ; 
/, leprous nodule about duct of sweat-gland; g, leprous foci in the neighborhood of swea^gland ; leprous 
focus having no especial relation with any of the specific skin structures ; i, foci of bacilU. X 32. 



sins), but no disease extending over a large area of the body can be pro- 
duced. Schottelius and Baumler inoculated apes subcutaneously with 
freshly excised pieces of leprous skin and with pieces of leprous tissue 
rubbed to an emulsion in warm bouillon and warm blood-serum, but 
obtained negative results. According to Campana and Wesener the 
bacilli are taken up from the inoculated pieces by wandering cells, but 
give rise to no specific infection and do not inultiply. Czaplewski was 
able to produce in rabbits, guinea-pigs, and mice by means of inocula- 
tions of cultures of the bacilli only slight and transitory inflammations. 

The infection of man takes place by a direct or indirect transfer from 
individual to individual. The nasal secretion is especially infectious 
(Sticker), particularly when leprous suppurations are present in the 



LEPROSY. 



641 



nose. In the case of leprous affections of the respiratory tract the spu- 
tum may contain bacilli ; and. in the formation of nodules and ulcers in 
the skin the secretions from the latter may also contain the bacilli. 
Contagion seems to result most frequently from the nose (Sticker) ; in 
favor of this view speaks the fact that the anterior nasal region is usu- 
ally involved very early. The bacilli are spread throughout the body 
chiefly by the lymphatic system ; but they may also get into the blood- 
stream. 

Besides the nose, the skin and the peripheral nerves are chiefly con- 
cerned in the disease ; but the bacilli may multiply in other tissues, as 




Fig. 489.— Leoutiasis leprosa. (After G. Munch.) 



in the testicles, liver, in the ganglia, and in the spleen, thereby giving 
rise to foci of disease in the organs. 

At the place of colonization the bacilli excite inflammation with tis- 
sue-proliferation. Granulation tissue containing blood-vessels is formed ; 
this remains for a long time in a condition which is characterized by 
great richness in cells, and forms the basis for nodules and tumors in 
the skin and nose and for spindle-shaj)ed thickenings of the nerves, and. 
is the cause of the irritation and later of the degeneration and destruc- 
tion of the nerve-fibres. The bacilli and the tissue-proliferations caused 
by their multiplication often group themselves in the skin about the hair- 
follicles (Fig. 488, d), the ducts (/), and the coil (g) of the sweat- 
glands, but such a relationship is not always to be seen (h). Moreover, 
the bacilli may penetrate into the blood-vessels, the hair-follicles, and 
sweat-glands (Touton), and thence on to the surface of the skin. Infec- 



M'2 THE PATHOGENIC FISSIOX-FUXGI. 

tion of the arterial walls causes a piolilei-aTiiig arteritis. l>y which the 
walls become greatly thickened and the luiuina narrowed. In the ner- 
A ous STStem tlie bacilli are found both in tlie connective tissue and in the 
nervous elements, particularly in the ganglion cells > Sudakewitsch ). 
The cells occuj^ied by them undergo degeneration in the eoui se of time,, 
occasionally with hydi'opic swelling and the formation of \'aeuoles. 

The tissue-proliferations caused by the growth of the bacilli may 
almost wholly disappear through the disintegration and absorption of the 
cells after the condition has lasted for years; but there always remair? 
indurations rich in cells and pigmentations in the skin. Caseation never 
takes i3lace. 

Leprosy of the sl-ijt occurs especially in the face, on the extensor sur- 
face of the knees and elbows, as well as on the back of the hands and 
feet. It begins with the formation of red spots which either vanish, lead - 
ing pigmented sjDots behind, or become elevated into nodules of a l;)rown- 
ish-red color (Jejyra tuherosa sire tuberculosa sire nodosa ). In the region 
of the red spots the tissue contains large numbers of bacilli < Philipson ), 
which for the most part lie within the vessels, and already at this stage 
the proliferation of the tissue can be deinonstrated. According to the 
investigations of Miiller the vesicular eruptions which occur in leprosy, 
and were formerly regarded as the secpielte of the leprous disease of the 
nerves, are caused by the presence of the bacilli. 

The nodules may remain unchanged for months, or they may increase 
in size and become confluent, so that very large protuberances may be 
formed, which, because of the distortion of the face therein' occasioned, 
ha\ e given occasion for the designation /Vfc^V.^ leontina (Fig. 489 \ 

Through ejcternal in fluences ulcers may be produced which show no 
tendency to healing. Xew nodules appear occasionally following ei'y- 
sipelatous reddenings and swellings of the skin. The glands of the sub- 
maxillary and inguinal region swell to form very large nodules. 

Leprosy of the nerres [lepra nerrorum sii^e anwsthetica) leads first to 
hyperoesthesi'a and pain, later to anaesthesia, more rarely to inotor paraly- 
ses in the region of the affected nerves. The further consequences of the 
disease of the nerves are disturbances which express themselves in the 
skin by the formation of white and brown spots {leimt maculosa, morphea 




Fig. 490.— Lepra ana>stiietica ulceiMsa of tlie leg and foot. (After G. Miincli.) 

nigra et alba), and in the bones and muscles by atrophy. Since those 
suffering from the disease are likely to injui^e themselves after the ap- 
pearance of anaesthesia, ulcers are often formed at a later period ( Figs, 
490, 491) which cause deep erosions and may lead to the loss of entire 
phalanges (lepra tnutilans). 



643 



LEPROSY. 



Leprosy of the skiu and of the nerves are usually combiued ; more 
rarely do they occur alone. Besides the nose, skin, and nerves, the cen- 




FiG. 491.— Lepra ani^stlietiea mutilans. Partial destructii >n * >!' the Uiifivi s ; ulcers in the hand. (After 

G. Miiuch.) 

tral nervous system, mucous membranes, cornea, the cartilages, liver, 
lungs, spleen, lymph-glands, and the testicles, become diseased. 

In Europe leprosy is confined mainly to Norway, Sweden, Finland, 
the Baltic Sea provinces of Russia, and the coasts of the Mediterranean ; 
but occurs sporadically in other regions. It occurs very frequently in 
Hindustan, China, Sumatra, Borneo, Java, and Mexico, on the northern 
and eastern coasts of South America, in Upper and Lower Guinea, in 
Cape Colony, and on the northern coast of Africa. 

Literature. 

(Lepra-haeilli. Leprosy. ) 

Arning': Lepraimpfung beim Menschen. Arch. f. Derm., 1889, Erganzungslieft ; 
Lepra mit besoud. Berucksiclit. der Uebertragung diircli Hereditat u. Contagion, 
lb., xxiii., 1891. 

Babes: Unters. lib. d. Leprabacilhis ii. d. Histologie der Lepra, Berlin, 1898 (Lit.); 
Kultur der von mir bei Lepra gef. Diphtheridee. Cbl. f. Bakt., xxv., 1899; Die 
Lepra, Wien, 1901. 

Babes et Kalindero : La lej^re en Roiimaine. Ann. de I'lnst. de path, de Boiicarest, 
i., 1890. 

Babes et Mosenna: La lepre puhnonaire. Arch, de med. exp., 1899. 



644 



THE PATHOGENIC FISSION- FUNGI. 



Berg-mann: Die Lepra in Livland, Stuttgart, 1897. 
Blaschko : Die Lepra im Ki eise Memel, Berlin, 1897. 
Bonome: Sulla lepra dei polmoni. Arch, per le Sc. Med., xii., 1888. 
Bordoni-XJffreduzzi : La coltivazione del bacillo della lepra. Arch. p. 1. Sc. Med., 
xii., 1888. 

Campana: (Impfungen). Arch. ital. de biol., iii., v.; Arch, per le Sc. Med., viii., 

1883; Vierteljahrsschr. f. Derm., xiv., 1887. 
Czaplewski: Aus einem Leprafall gezlichtete Bacillen. Cbl. f. Bakt., xxiii., 1898. 
Damsch.: Uebertragungsversuche v. Lepra auf Thiere. Virch. Arch., 92 Bd., 1883. 
Doutrelepont u. Wolters: Viscerale Lepra. Arch. f. Derm., 34 Bd., 1896. 
Ehlers : Aetiol. Studien uber Lepra, Berlin, 1896. 

Gerlach: Die Bezieliimgen zwischen Hautfleckeu u. d. Nervenerkrankung bei Lepra 

anaesthetica. Virch. Arch., 125 Bd., 1891. 
Hansen, Armauer: Bacillus leprae. Virch. Arch., 79, 80, 114, 120 Bd., 1880-90. 
Joseph: Viscerale lepra. Arch. f. Derm., 43 Bd., 1898. 

Kuhne: Zur pathol. Anat. d. Lepra. Monatsh. f. prakt. Derm., Erganzungsh., iii., 
1887. 

Leloir: Traite pratique et theorique de la lepre, Paris, 1886. 
Lie: Zur pathol. Anat. der Lepra. Arch. f. Derm., 29 Bd., 1894. 

Melcher u. Orthmann: Experiment. Darm- u. Lymplidrlisenlepra der Kaninchen. 

Berl. klin. AVoch., 1885. 
Miiller: Lepra. Deut. Arch. f. klin. Med., xxxiv., 1884. 
Miinch: Lepra u. Vitiligo im Sliden Russlands, Kiew, 1884-86. 

Neisser: Bacillus leprae. Bresl. arztl. Zeitschr., 1879; Virch. Arch., 84, 103 Bd. ; v, 
Ziemssen's Handb. d. spec. Path., xiv. ; Structur d. Lepra-bacillen u.-Zellen. Cbl. 
f. a. Path., i., 1890. 

Philippson: Histologic d. hyperam. Flecke d. L. tuberosa. Virch. Arch., 132 Bd. ; 

Symbiose d. Tuberkelbacillen mit Leprabacillen. lb., 132 Bd., 1893. 
Prus: Verhalten d. Morvan'schen Krankh. zur Lepra. Arch. f. Psych., 27 Bd., 1895. 
Ramon y Cajal: Sobre las celulas gigantes de la lepra. Caceta Sanit. de Barcelona, 

ii., 1890. 

Rickli: Zur pathol. Anatomic d. Lepra. Virch. Arch., 129 Bd., 1892. 
Scheube : Die Kraukheiten der warmen Lander, Jena, 1900. 
Sokolowsky: Zur pathol. Anat. d. Lepra. Virch. Arch., 159 Bd., 1900. 
Sticker: Lepra. Miinch. med. Woch., 1897; Arb. a. d. K. Gesundheitsamte, xvi., 
1899. 

Sudakewitsch : Zur pathol. Anatomic d. Lepra. Beitr. v. Ziegler, ii., 1887. 
Teich: Kultur d. Leprabacillus. Cbl. f. Bakt., xxv., 1899. 

Thoma: Anatomisches lib. Lepra. Virch. Arch., 75 Bd., 1871; Deut. Arch. f. klin. 
Med., 47 Bd., 1891. 

Touton: Topographic d. Leprabacillen in d. Haut. Virch. Arch., 104 Bd., 1880 
TJh.lenhut u. Westplial: Histol. d. Lepra tuberoso-anaestlietica. Cbl. f. Bakt., xxix., 
1901. 

Unna: Leprastudien. Monatsh. f. prakt. Derm., Erganzungsh., 1885; Dermat. Stu- 
dien, i., Hamburg, 1886. Deut. med. Woch., 1886; Virch. Arch., 103 Bd., 1886. 

Virchow: Die krankh. Geschwulste,- ii. ; Lepra d. Milz. Berl. klin. AVoch., 1885. 

Vossius: Uebertragbarkeit d. Lepra auf Kauinchen. Ber. d. Ophthal. Ges. in Heidel- 
berg, xvi., 1884. Zeitschr. f. vergl. Augenheilk., vi., 1889; Beitr. v. Ziegler, viii., 
1890. 

Wesener: Zur Uebertragbarkeit d. Lepra. Beitr. v. Ziegler, vii. , 1890. 

Wolters: Der Bacillus leprae (zusammenfassender Bericht). Cbl. f. Bakt., xiii., 1893. 

See also the Mittheil. u, Verhandl. d. Le praconferenz, Berlin, 1897; and the Zeitschr. 
" Lepra, " edited by von Ehlers, appearing since 1900, in Leipzig. 

§ 170. The Bacillus mallei is a bacillus discovered by Loffler, Schiitz, 
and Israel in glanders foci ; and later confirmed and studied by Weichsel- 
baum, Kitt, and others. It is to be regarded as the cause of glanders 
(malleus, maliasmus) and of farcy (sMn glanders, malleus farciminosus), a 
contagious disease of horses, which occurs in man chiefly through trans- 
mission from horses. 

The glanders bacilli are very small, slender rods, which occur in the 
diseased foci, sometimes scattered, sometimes lying together in small 
clumps. Alkaline methylene -blue or gentian -violet are employed espe- 
cially for their staining. 



GLANDERS. 



645 



The stained bacilli often show clear spots, which have been regarded 
by many observers as spores, but by Loffler as evidences of degeneration. 
The bacilli are present chiefly in the glanders -foci, but at times appear in 
the blood of the atfected individual (Loffler, Kitt). 

The bacilli grow at a temperature of 30°-40° C, ui3on coagulated 
blood-serum, as well as upon slices of boiled potato, and upon potato- 
pap. Upon the latter they form amber-yellow coatings that later be- 
come red. Upon blood-serum they form small yellowish transparent 
drops which later become milky white. Upon agar the colonies are 
grayish -white. In cultures club-shaped forms and threads are not infre- 
quently seen. Spore-formation has not been demonstrated. 

Horses, asses, sheex^, young dogs, goats, cats, guinea-pigs, and field- 
mice are suitable for inoculation. In cats, after inoculation, there 
develop in the testicles cellular foci consisting essentially of leucocytes 




Fig. 493.— Glanders of a cat's testicle (Miiller's fluid, haematoxylin) . a, Seminiferous tubules; b, c, 
tubules filled with leucocytes ; d, foci of leucocytes in the connective tissue. X 90. 



(Fig. 492), which lie partly inside the canaliculi (h, c) and partly around 
them {d). The injection of the pus of glanders into the peritoneal cav- 
ity of male guinea-pigs causes the testicles to swell rapidly (Straus). 
After subcutaneous inoculations ulcers develop at the seat of inocula- 
tion, followed by swelling of the neighboring lymph-glands. Later, nod- 
ules may develop in the internal organs, and ulcers may be formed in 
the nose. Typical glanders may be produced in horses and asses. Cattle, 
white mice, and house-mice are immune. 

The usual atrium of infection in horses is the mucous membrane of 
the nose ; following this is the involvement of the submaxillary glands, 
and further a metastasis in various organs. In the nasal mucosa there 
arise as the result of the infection either diffuse cellular infiltrations of 
the mucosa or subepithelial nodules of the size of a millet-seed or a pea. 
34 



646 



THE PATHOGENIC FISSION-FUNGI. 



In chronic farcy of the skin larger nodules are developed which join to- 
gether in rows, forming worm-like cords. 

The nodules of the mucous membrane break down easily. The cells 
of which they are comi^osed bear precisely the character of pus^corpus- 
cles. Through the disintegration, softening, and suppuiation of the 
nodules ulcers with yellowish intiltrated bases are formed. These en- 
large through a progressive, nodular or more diffuse infiltration and 
subsequent disintegration of the edges of the ulcer, as well as through the 
confluence of neighboring ulcers. Horses dying of glanders often present 
in the mucosa of the nasal septum very extensive irregularly shaped, 
sinuate ulcers, with eroded edges and floors covered with gray and yel- 
lowish material. In addition to these there are numerous small, lenticu- 
lar ulcerations and gray or yellowish nodular foci which are on the point 
of breaking down. The whole process is closely related to purulent in- 
flammation. The healing of the idcer is characterized by the formation 
of radiating scars. 

The cervical lymph-glands are constantly swollen and inflamed. Of 
the internal organs the lungs especially are involved. They contain 
either nodules having a caseated and disintegrated centre and a grajash 
cellular periphery, or foci of lobular pneumonia, w^hich x)resent either a 
clear gray or a more h^emorrhagic appearance, or through fatty and 
cheesy metamorphosis become opaqiie and yellowish- white. Occasionally 
the mucosa of the alimentary tract contains nodules of varying size, in 
part clear gray and consisting of cellular tissue, in part opaque yellow- 
ish-white, undergoing caseation or approaching suppuration. The 
spleen, liver, kidneys, and bone-marrow may also contain nodules. 

In farcy, which runs a more chronic course than glanders, there are 
formed in the skin and muscles nodules consisting of a small -celled tissue 
which later undergoes retrogressive metamorphoses, caseates and divsin- 
tegrates. 

In man an infection with glanders takes place usually through 
small wounds of the skin, but may also occur primarily in the mucous 
membranes adjacent to the skin. In the skin and subcutaneous tissue it 
gives rise to nodular, i^ustular exanthemata, carbuncular and phlegmon- 
ous inflammations which may result in supx^uration, and to purulent in- 
flammations of the lymph-vessels and lymph-glands. In the mucosa of 
the respiratory tract catarrhs are produced and suppurating nodules and 
nodes are formed, leaving ulcers behind. In the internal organs metasta- 
tic small-celled nodules are formed, showing a tendency to suppuration ; 
also extensive abscesses and purulent infiltrations, especially in the mus- 
cles. In chronic farcy which may last for years, large nodules are occa- 
sionally formed in the skin and muscles which through disintegration 
give rise to ulcers which heal with difficulty. For the diagnosis of the 
condition the bacteriological examination and inoculation exx^eriments are 
necessary. 

According to the iiivestigatlous of Kalning, Prensse, and others, an active poison. 
malleln, maybe extracted from cultures of glanders bacilli which, when injected in 
small doses into horses sick of glanders, causes a febrile rise of temperature, and may 
be used as a diagnostic aid. 



GLANDERS. RHIN0SCLP:K0MA. 



647 



Literature. 

{Glanders and tlic Ghmders-bacillus.) 

Babes: Observations sur lu morve. Arch, de med. exp., iii., 1891. Ann. de I'Inst. de 

path, de Boucarest, ii., 1893, vi., 1898. 
V. Baracz: Chron. Rotz beim Menschen. Virch. Arch., 159 Bd., 1900. 
Bass: Die Rotzkrankheit der Pferde. Deut. Zeitschr. f. Thiermed., xix., 1893 (Lit.). 
Baumg-arten : Zur Frage der Sporenbildung bei Rotzbacilleu. Cbl. f. Bakt., iii., 1888. 
Bolling'er; v. Zienissen's Handb. d. spec. Path., 3 Bd. 

Bordoni-Ufireduzzi : Ueber die Kultur der Rotzbacillen. Zeitschr. f. Hyg., iii , 1888. 
Buschke: Chron. Rotz d. Haiit d. Menschen Arch. f. Derm., 36 Bd., 1896. 
Cadeac et Malet Et. exper. de la transmission de la morve. Rev. de med., vii., 1887. 
Coleman and Ewing: SepticcTmic Glanders in the Human Subject. Jour, of Med. 
Res., 1903. 

Duval: Morve humaiue Arch, denied exp., 1896. 

Eber: Ueber Rotzlymphe (Mallein). Cbl. f. Bakt., xi., 1892. 

Ehrich: Rotz beim Menschen. Beitr. v. Bruns, xvii., 1896. 

Finger: Zur Frage der immunitat u. der Phagocvtose beim Rotz. Beitr. v. Ziegler, 

vi. ,1889 

Foth: Das Mallein. Fortschr. d. Med., xiii., 1895. 

Frothingham The Diagnosis of Glanders bv the Straus Method. Jour, of Med. Res., 
1901. 

Galli- Valerio . La morphologic du B. mallei. Cbl. f. Bakt., xxviii., 1900. 
Glaser: Ueber die Rotzkrankheit beim Menschen, I.-D , Breslau, 1876. 
Hartge: Ein Fall von Malleus humidus beim Menschen. St. Petersb. med. Woch., 
1890. 

Jakowski: Chron. Rotz beim 3Ienschen. Zeitschr. f. klin. Med., xvii., 1891. 

Johne: Mallein-Rotzimpfungen bie Pferden. Deut. Zeitschr. f. Thiermed , xix., 1893. 

V. Kahlden; Rotz. Eulenburg's Realencyklop.. xx., 1899 (Lit). 

Kernig: Ein Fall v. chronischem Rotz beim Pferde. Zeitschr. f. klin. Med , xiii., 1887. 

Kitt: Impfrotz bei Waldmalisen. Cbl. f. Bakt., ii.. 1887. 

Kranzfeld: Zur Kenntniss des Rotzbacillus. Cbl. f. Bakt., ii., 1887. 

Kiittner: Rotz beim Menschen. Virch. Arch., 39 Bd., 1867. 

Leclainche et Montane: Anat. Path, de la morve pulmonaire. Arch, de ITnst. P., 

vii. , 1893. 

Lofler: Die Aetiologie der Rotzkrankheit. Arb. a. d. Kais. Gesundheitsanite, i., 1886. 
Marx: Morphologic d. Rotzbacillus. Cbl. f. Bakt., xxv., 1899. 
Mayer: Rotzbacillus u. Rotzknotchen. Cbl. f. Bakt., xxvii., 1900. 
Pflug: Zur pathol. Zootomie d. Lungenrotzes, Leipzig, 1877. 
Remy: Morve chronique de I'homme. Arch, de med. exp., ix., 1897. 
Straus. Essais de vaccination contre la morve. Arch, de med. exp., i., 1889. 
Tedeschi: Rotzmeuingitis. Virch. Arch., 130 Bd., 1892; Wirkung d. Einimpfung d. 
Roztes in die Nervencentra. Beitr. v. Ziegler, xiii., 1893. 

§ 171. As the Bacillus of rhinoscleroma, Frisch, Pellizari, Chiari, 
Cornil, Alvarez, Kobuer, Paltauf, von Eiselsberg, Dittrich, and others 
liave described a bacillus with rounded ends, which is constantly present 
in the diseased condition known as rhinoscleroma or scleroma respiratorium 
(Bornhaupt, Wolkowitsch), and is therefore regarded as the cause of the 
same. It stains best with methyl -violet, the sections being left in the 
stain for twenty-four to forty-eight hours. After staining, the sections 
are treated with iodine water, or left in absolute alcohol for one to three 
days. 

The bacilli for the chief part have a hyaline capsule. According to 
Paltauf, von Eiselsberg, Dittrich, Wolkowitsch, and others they may be 
cultivated upon blood-serum, gelatin, agar-agar, and potatoes, and also 
form capsules in the cultures. When grown in bouillon they show on 
the contrary no capsules (Dittrich). Stab-cultures in gelatin resemble 
closely the nail-cultures of the Friedlander pneumonia-bacillus, but are 
of a translucent grayish-white and not dead white. The bacilli stain 



648 



THE PATHOGENIC FISSION-FUNGI. 



more easily than the pneumonia bacilli, and also stain by Gram's method. 
Stepanow observed, in inoculations into the eyes of guinea-pigs, progres- 
sive inflammations and proliferating granulations containing the bacilli 
and hyaline degenerated cells. 

Rhinoscleroma occurs chiefly in eastern Austria and southwestern 
Eussia ; isolated cases have been observed also in Silesia, Italy, Egypt, 
Belgium, Sweden, Switzerland, and Central America. It is a chronic 
disease progressing for years, beginning in the nose (Wolkowitsch), more 
rarely in the pharynx, larynx, or palate, and extending thence to neigh- 
boring parts — the external nose, lips, lachrymal duct, trachea, etc. In 
the nose the disease is characterized by a thickening of the nasal wall 
which is sometimes diffuse, sometimes elevated or nodular. The exter- 
nal skin takes on a red or brownish- red color, becomes stiff and fissured 
and covered with scales. In the throat and respiratory tract dense, car- 
tilage-like infiltrations are sometimes present, at other times a contract- 
ing cicatricial tissue is formed. The infiltrations may appear in the 
form of nodes and nodules or as elevations and flattened areas of 
thickening, or they may be spread out more diffusely. By the transfor- 
mation of the ijifil [ration into scar tissue marked deformities of the 




Fig. 493. FIG. 494. 



Fig. 493.— Section of rhinoscleromatous tissue, with numerous degenerated and vacuolated cells contain- 
ing bacilli (osmic acid, hasmatoxyiin) . Preparation by Stepanow. X 340. 

Fig 494 —Cells in condition of hyaline degeneration, and hyaline spherules, from rhinoscleromatous 
tissue of the' vocal cord and of the nose. Preparation by Stepanow. a, b, c, d, Hyaline-degenerated cells 
containing small bacilli; e, hyaline cells with encapsulated bacilli; /, cells with hyaline spherules; h, 
free hyaline spherules, a, b, c, d, Stained with Loffler's solution ; e, with hsematoxylin ; /, g, h, with fuch- 
sin. X 425. • 

affected organs may be produced. Deep destruction of the tissues is 
absent ; superficial ulcerations may, however, occur. On section the infil- 
trated tissue appears yellowish, spotted, but not infrequently shows a 
gray or grayish-red color. The tissue of the affected areas consists partly 
of granulation tissue, partly of fibrous connective tissue. If the former 
extends to the epithelial covering there appear in part proliferations, in 
part degenerative processes in the epithelial cells, the latter being char- 
acterized by the formation of vacuoles and by an infiltration of the part 
with round cells. According to Stepanow the vacuoles may contain 
bacilli. 

The granulation tissue itself shows in many places no especial pecu- 
liarities; rather does it present the same conditions present in other 
inflammatory infiltrations and proliferations of connective tissue. In 
other places, on the contrary, there may be found a larger or smaller 
number of large connective-tissue cells containing one vacuole or show- 
ing a total vacuolar degeneration or a reticulated structure, in the meshes 



RHINOSCLEROMA. ACTINOMYCOSIS. 



649 



of which bacilli may be demonstrated (Fig. 493), some of the latter pos- 
sessing capsules. It cannot be doubted that the multiplication of the 
bacilli in the cells is the cause of the cell -degeneration. 

Besides the cells showing vacuolar degeneration there also occur cells 
of various shapes which have undergone hyaline change (Fig. 494, a, h, 
c, d, e). These also contain bacilli with and without capsules, and also 
coccus-like forms. Through the loss of their nuclei these cells may 
become converted into non-nucleated homogeneous lumps {d). Finally, 
there also occur cells which enclose hj^aline spherules (/, g), and free 
spherules are also found lying in the tissues (Ji). In places not yet 
affected by cicatricial retrogression the hyaline formations may be pres- 
ent in large numbers. 

Literature. 

(Ehinoscleroma. ) 

Alvarez. Recli. snr I'anat. pathol. du rhinosclerome. Arch, de phys., vii., 1886. 
Bender: Das Rliinosklerom. Cbl. f. Bakt., i., 1887. 

Chiari: Stenose des Kehlkopfes u. des Larynx bei Rliinosklerom. Wien. med. Jahrb., 
1882. 

Cornil: Legons prof. pend. le I. sem. de I'an., 1883-84, Paris, 1885. 
Cornil et Alvarez: Mem. p. serv. Si I'hist. du rhinosclerome. Arch, de phys., vi., 
1*885. 

Dittrich: Ueber das Rhinosklerom. Zeitschr. f. Heilk., viii., 1887; Zur Aetiologie 

des Rhinoskleroms. Cbl. f. Bakt., v., 1889; Zeitschr. f. Heilk., viii. 
Frisch: Zur Aetiologie des Rhinoskleroms. Wien. med. Woch., 1882. 
Jaffing-er: Das iSklerom d. Sclileimliaut d. Nase, etc., Wien, 1892. 
V. Marschalko: Histol. d. Rhinoskleroms. Arch. f. Derm., 53, 54 Bd., 1900. 
Mibelli: Beitr. z. Histologic des Rhinoskleroms. Monatsh. f. prakt. Derm., viii., 1889. 
Mikulicz: Ueber das Rhinosklerom. Langenbeck's Arch., 20 Bd., 1876. 
Nikiforoff: Ueber das Rhinosklerom. Arch. f. exp. Path., xxiv., 1888. 
Paltauf: Aetiologie des Skleroms Wien. med. Woch., 1891, 1892. 

Paltauf u. V. Eiselsberg: Zur Aetiologie des Rhinoskleroms. Fortschr. d. Med., 1886. 
Pawlowsky : Ueb. d. Aetiologie des Rhinoskleroms. Cbl. f. allg. Path., i., p. 601. 
Pellizari: II Rinoscleroma, Firenze, 1883. 
Rpna: Rhinosklerom. Arch. f. Derm., 49 Bd., 1899. 

Stepanow: Ueber die Impfungen des Rhinoskleroms. Cbl. f. Bakt., v., 1889; Zur 

Aetiologie des Skleroms. Monatsschr. f. Ohrenheilk., 1893. 
"Wolkowitsch : Das Rhinosklerom. Langenbeck's Arch., 38 Bd., 1889. 
Zagari: Ricerche etiol. sul Rinoscleroma. Giorn. internaz. d. Sc. Med., 1889. 

§ 172. The Actinomyces or ray=fungus is a polymorphous fission- 
fungus wliich appears in different forms of growth in the human and 
animal organism as well as in cultures. It is the cause of actinomycosis, 
a disease occurring in man as well as in cattle, swine, and horses, and 
characterized by a progressive inflammation that produces in part granu- 
lation tissue and connective tissue, and in part pus. The botanical posi- 
tion of the fungus is still unsettled. By many it is classed with the 
thread-fungi, others group it with the polymorphous bacteria. Bostrom 
places it in the group cladothrix ; Kruse, in the group streptothrix. 

The masses of fungus formed in the tissues by the organism were long 
ago observed by Langenbeck and Lebert, but their significance was not 
rightly interpreted. The observations of Hahn, supplemented by those 
of Bollinger and Harz, first led to a correct interpretation of the ray- 
fungus occurring in domestic animals. Israel shortly after found a simi- 
lar fungus in man ; and Ponfick soon after gave his opinion in favor of 
the identity of actinomyces of cattle with the fungus discovered by Israel 
in man. 



650 



THE PATHOGENIC FISSION-FUNGI. 



According to tlie investigations of Bostrom actinomyces differs from 
the bacilli in the fact that in cultures ui^on beefs-blood serum or agar it 
forms branching threads. The 
threads of the cultures are partly 

straight, partly wavy, at times ^i^^'^^^^^s^^^tS^^as^^^^* 
also twisted spirally. They 
break up by transverse division 





Fig. 495. 

¥iG. 4:95.— Actinomyces hominis. Teased preparation. X 700. 



Fig. 496. 



Fig. 496. — Actinomycosis of the tongue (alcohol, alum carmine.) o, Actinomyces druse; b, c, cellular 
nodules ; d, transverse section of muscle ; e, /, connective tissue with blood-vessels. X 175. 



into short rods and coccus-like forms, which under suitable conditions 
again grow into threads. 

Within the human and animal organism the fungus appears in masses 
in the form of little granules scarcely recognizable by the naked eye, or 




in spherules up to 2 mm. in diameter. These are sometimes colorless 
and transparent, at other times white and opaque, sometimes yellow, or 
brown, or green and yellowish-green. Many of the smaller ones consist 



ACTINOMYCOSIS. 



651 



only of a feltwork of fine, partly branched threads, some of which are 
straight, or wavy, or twisted. 

The majority of the granules contain, moreover, peculiar club-shaped 
structures (Fig. 495), which form the ends of the threads, and if present 
in large numbers, as is the case particularly in the larger granules, have 
a radial arrangement (Figs. 496, a, 497, a), and so give to the colony of 
the fungus a ray-like appearance. Occasionally hand- or fan-like forms 
develop on the ends of the threads. According to Bostrom all these 
peculiar structures are due to a swelling of the membrane of the threads, 




Fig. 498.— Actinomycosis of the lung (alcohol, carmine. Gram's), a, Fungus druse; &, small-celled 
nodule ; c, fibrous tissue ; d, alveoli filled with large and small cells ; e, bronchiole with wall inflltrated 
with cells ; /, small-celled focus in the neighborhood of the bronchus (e) ; alveoli filled with vascularized 
connective tissue ; ft, connective tissue growing into the alveoli ; % blood-vessels of the lung tissue ; 
?c, blood-vessels of the inflamed area. X 43. 

and are to be regarded as retrogressive changes resulting from an ex- 
haustion of the food-supply. 

The actinomyces is usually taken into the body with the food or the 
respired air, and finds its first development often in the mouth. Since 
the threads and granules of actinomyces in many respects correspond 
closely to the form of fungus known as leptothrix, which is frequently 
found in the mouth cavity, the latter also forming club -like swellings on 
the ends of the threads (Israel), it is difficult to determine the presence 
of actinomyces in the mouth, in which situation, moreover, it appears 
not to form the characteristic granules. The fungus has not yet been 
demonstrated outside of the animal organism. It must be remarked that 
very often bits of higher plants (beard of wheat, splinter of wood) have 



652 



THE PATHOGENIC FISSION-FUXGI. 



been found in the pus of actinomycotic foci, and that the swallowing of 
portions of plants (spike of grain [Bertha]), or the contamination of 
wounds with vegetable material, have in certain cases preceded the de- 
velopment of actinomycosis. It is, therefore, very probable that the 
fungus is present upon the higher plants or upon wood. 

If the ray-fungus succeeds in settling in a tissue it excites an inflam- 
mation in its neighborhood. While the fungus which has penetrated 
into the tissue develops a mycelium and a fungus -granule (Figs. 496, «, 
497, a, 498, a) there is formed in its neighborhood a nodular focus of 
inflammation, which at first consists of small round cells (Figs, 496, h, 
c; 498, &) ; but later, in addition to pus-corpuscles (Fig. 497, c), also con- 
tains epithelioid cells and giant -cells (J), d). 

The fungus-granules may increase within the nodule and lead to its 
enlargement ; and it very often happens that cellular nodules the size of 
a pea and larger contain a large number of fungus-foci, which are usually 
situated in the periphery of the same. At the same time new fungus- 
foci, and consequently new cellular foci, may appear in the neighborhood. 
The further spread of the infection takes place by means of small rods 

and threads, which are broken off 
from the larger masses, and may 
be seen in the tissues partly free 
and partly enclosed in cells. 

Larger nodules often undergo 
in time a purulent liquefaction of 
their central portions, leading to 
the formation of small abscesses, 
which may become confluent to 
form larger jyus-cavities or sinuses. 
In the neighborhood of the ceUular 
areas (Fig. 498) there develops 
early an actiye proliferation of tissue, 
which leads to the formation of ves- 
sels (A-) andjoung granulation tissue, 
which later becomes transformed 
into connective tissue (c, g, h). If 
the connective -tissue proliferation 
attains very considerable i)ropor- 
tions, it leads to an induration (Fig. 
498), often also to an enJargement of the tissue. The connective-tissue 
proliferation may finally extend into the small- celled areas, and replace 
the latter, the fungi probably being destroyed in this way. 

If the connective -tissue x)roliferation becomes predominant there 
arises in the course of weeks and months a nodular formation of tissue 
(Fig. 499, a) which in cattle may attain the size of a man's fist or even 
reach a much greater size. The tumor consists partly of dense connec- 
tive tissue, partly of granulation tissue, and partly of intermediate 
stages between the two. It always contains small cellular foci or even 
cavities due to disintegration, in the purulent contents of which the 
fungus-masses are found in the form of the granules described above. 
When the fungus develops within the jaw-bone there occurs at the 
same time an active new-formation of bone at the periphery (Fig. 
499, a) of the process. 

A predominance of tissue -necrosis and of suppuration over tissue - 
production gives rise to more or less extensive sinuous cavities and 




Fig. 499.— Frontal section tliroug'ti tlie nose and 
upper jaw of a steer affected with a tumor-Like 
actinomycosis, a. Nodules consistiner of connective 
tissue, bone, and small pus foci. One-fourth nat- 
ural size. 



ACTINOMYCOSIS. 



653 



branching fistulous tracts communicating with one another. The walls 
of these consist of granulation-tissue and hyperplastic connective tissue, 
and here and there contain fungus foci. The masses of fungi may in 
part become calcified. 

In cattle the disease affects chiefly the lower jaw, but may involve 
also the upper jaw (Fig. 499, a), the tongue, throat, larynx, oesophagus, 
stomach, intestinal wall, skin, lungs, and subcutaneous and intermuscular 
tissues. In these regions it leads to the formation of more or less exten- 
sive nodular tumors of the character described above, and was formerly 
given various names, such as osteosarcoma, bone-cancer, bone-tuberculo- 
sis, lumpy jaw, wooden tongue, tuberculosis of the tongue, lymphoma, 
fibroma, worm-nodules, etc. In man the infection, so far as is known, 
takes place through the mouth, fauces, oesophagus, stomach, intestine, 
and lung, or through some external injury. In the first -named region an 
infection of actinomyces may take its start from carious teeth (cavities 
or fistulie), or from any injury to the soft parts of the jaw or cheek. 
Thence it spreads over the neighborhood and may finally involve the face 
and the hairy portions of the head, as well as the throat, neck, back, and 
breast. 

With the advent of the process there arise swellings which later 
soften and give fluctuation. When the latter is the case, pus is formed 
which is at times thin and watery, at other times more viscid, and con- 
tains the characteristic granules. If these abscesses break externally there 
may be formed fistulous tracts, which may either close again, or continue 
to secrete pus. 

Besides these purulent foci, which sometimes are small, at other times 
extensive, there is constantly formed more or less granulation tissue, 
which at times may be very abundant. As a result of fatty degeneration 
and disintegration of its elements the granulation tissue often becomes 
partially whitish or yellowish or reddish-white in color, and permeates 
the diseased tissue in an irregular manner. In other places it comes to 
a develox^ment of connective tissue, particularly in those places where 
the process is not spreading. 

Through this development of connective tissue a local healing result- 
ing in cicatricial indurations may take place, but in other parts the process 
usually makes further progress and may under certain circumstances lead 
to very extensive destruction. If the disease encroaches upon the bones 
of the spinal column or of the thorax these may be gradually destroyed 
from the surface, and become rough, eroded, and carious. In rare cases 
the jaw-bone may be attacked from within through an alveolar process, 
and so undergo destruction. From the base of the skull the process may 
extend into the interior of the skull and lead to actinomycotic meningitis 
and encephalitis. 

In primary infection of the respiratory apparatus the process takes 
the form of a bronchopneumonia characterized by the formation of nod- 
ular foci (Fig. 498, h) the central portions of which at an early stage 
assume a yellowish -white color. Through the disintegration of the in- 
flammatory foci cavities may be formed which contain fluid, pus-corpus- 
cles, fatty detritus, spherules of fatty granules, disintegrated red cells, 
and masses of actinomyces. The tissue lying between the mycotic foci 
suffers a more or less extensive, often very marked, inflammatory thicken- 
ing and induration (Fig. 498, c), and through a new-formation of con- 
nective tissue may be transformed into a callous, slate -gray or gray and 
white mass, devoid of air, and later undergoing cicatricial contraction. 



654 



THE PATHOGENIC FISSION-FUNGI. 



In this manuer a large i^ortioii of the lung may Ijeconie converted into a 
jnass of connective tissue. 

From the lung the process sooner or latei* extends to the visceral 
pleura, and from this to the costal pleura or to the pericardium, giving 
rise in these places to inflammatory exudations and proliferations of tis- 
sue, which may lead to adhesions between the opposite layers of the 
pleura or pericardium. From the costal i^leura the cellular infiltration 
as well as the pus formation and the fatty degeneration and disintegra- 
tion of the granulation tissue may extend between the ribs to the out- 
side, and spread in the contiguous soft parts, in the connective tissue 
and muscles, and may finally break through in places. From the 
lungs a rupture may sometimes take i^lace into the mediastinum or 
pericardial sac, and finally into the heart. Under certain conditions a 
rupture may occur through the diaphragm into {he abdominal cavity, or 
the process may extend from the posterioi' mediastinum into the retro- 
peritoneal connective tissue. 

The secondary areas of destruction lying outside of the lung often ■ 
reach an extremely large size, while in the lung the primary process 
advances but little and undergoes cicatrization. At one time the puru- 
lent softening predominates, at another time the formation of granulation 
tissue and the induration. 

Primary actinomycosis of the intestinal tract begins with the forma- 
tion of plaque -shaped whitish patches of the fungus (Chiari) or of nodu- 
lar mucosal and submucosal foci (Zemann), which contain the specific 
fungus, and lead to ulceration through the occurrence of disintegration. 
From the intestine the process spreads over the peritoneum and the retro- 
peritoneal connective tissue, as well as to the organs adjacent to the pri- 
mary focus — for example, the liver ; and may finally break through the 
abdominal wall. At the places where the fungi develops the prolifer- 
ating foci of inflammation described abo^^e are produced. If fsecal 
masses gain access to the tissues in case of intestinal rupture, gangrenous 
abscesses will arise. 

Metastasis may be associated with the local progression of the disease, 
but is rather rare. It usually results from a direct rupture into a blood- 
vessel. The metastases arising from a j)rimary focus in the intestine are 
found especially in the liver ; those arising from a primary focus in the 
lungs are found in the skin, muscles, bones, brain, intestine, and kidneys. 
The metastatic nodules behave like the primary foci. In rare cases there 
occur also primary foci of actinomycosis in the internal organs — for ex- 
ample, in the brain and liver. The portal of entrance in these cases maj' 
not be demonstrable. 

Johne, Ponfick, Bostrom, Wolff, and Israel have attempted inocula- 
tion experiments upon animals, and according to their reports have 
obtained positive results in x^art (Johne, Ponfick, Wolff, and Israel). 
Wolff and Israel, by the inoculation of rabbits and guinea-pigs, obtained 
in almost all cases a characteristic disease with the formation of inflam- 
matory foci containing the fungus-masses. They were also able to again 
cultivate upon agar-agar the fungus contained within these foci. 

Levy, as well as Kruse, assumes that there are two forms of actinomyces, an aUrobk- 
cultivated by Bostrom, and an aerobic cultivated by Wolff, Israel, Aschoff, and himself, 
the two forms being closely related. An attempt by Levy to change one form into the 
other was not successful, although the aerobic form could be made to grow under 
anaerobic conditions. He regards the actinomyces as well as the fine-threaded fungus 
known as streptothrix as belonging to a group, the Hyphomycetes. cliaracterized by the 



I 



ACTINOMYCOSIS. 655 

foniiatiou of branching, probably unicellular niycelia and which multiplies through an 
acrogenic snaring-olf of conidia-chaius or through fragments of threads resembling ba- 
cilli. Since the ray-fungi do not correspond to any one of the known hyphomycetes- 
groups, he places them in a separate group, the Actinomycetes. In this group he also 
])laces the tubercle-bacillus, the lepra-bacillus, the diphtheria-bacillus, and the bacillus 
of glanders. Lubarsch regards the streptothrices, with which he classes the ray-fungi 
(to which the tubercle-bacillus also belongs), as a transition form between the bacilli and 
the moulds. 

Berest/mc also distinguishes different forms of actinomyces (cultivated by him from 
straw, hay, etc.), and, in addition to octinornycosis, recognizes a condition of pseudo- 
actiiiomycosis, which runs a similar course to that of the former, but is caused by fungi 
which do not belong to the ray-fungi. Kruse likewise regards the etiological factor of 
an actinomycosis as being of varied nature and not representing a definite entity. 
Seharmayer emphasizes the variability of actinomyces according to the conditions of 
growth. 

OozzoUno found in the pus of a skin affection resembling actinomycosis granules 
and bacilli, from which a spore-producing bacillus (SaaY^us/tome/i^osMs) was cultivated, 
which produced no branching threads. 

Recently Eppinger (" Ueber eine neue pathogene Cladofhrix und eine durch sie her- 
vorgerufene Pseudotuberculosis," Beit. z. path. Anat. 'c. Ziegler, ix., 1891) found, in the 
pus of an old brain-abscess causing death through meningitis, a polymorphous fission- 
fungus, which he designated as Cladothrix asteroides. Its characteristics were deter- 
mined by cultivation and by inoculation into animals. Since the changes occurring in 
the lungs and bronchial glands of the affected individuals resembled those of tuberculo- 
sis, and as a disease suggesting tuberculosis resulted from the inoculation of this fungus 
into guinea-pigs and rabbits, the disease caused by the fungus may be designated pseu- 
dotuberculosa cladotrichica. 

Buchlioltz ("'Ueber mensclienpathogeue Streptothrix," Zeits. f. Hyg., xxiv., 1897) 
found in a pneumonic lung containing a large disintegration cavit}^ with ragged walls, 
that the diseased lung-tissue was infiltrated with fine, branching, and many times broken 
threads, which stained with Gram's method. He regarded the fungus, which he was 
not able to cultivate, as a pathogenic streptothrix. 

According to Bunker {Zeitschr. f. Mikroskopie und Fleischschau, iii., 1884) and Hert- 
iHg {Arch. f. wlssensch. u. prakt. Thierheilk., xii., 1886) there occurs in hogs a ray-fungus 
which is always situated in the muscles, particularly in the diaphragm, abdominal and 
intercostal muscles, and causes a degeneration of the muscle fibres in its neighborhood 
and proliferation of the intermuscular connective tissue. The fungus-masses form 
radially arranged clubs. They readily undergo calcification and then form white 
points in the flesh. 

According to investigations by Kanthack ("Madura Disease and Actinomyces," 
Jour, of Path., 1892), Boyce ("Upon the Existence of More than One Fungus in Ma- 
dura Disease," Trans. Phil. Boc, vol. clxxxv., 1894; Hyg. Bundschau, 1894). and Vin- 
rent ("Et. sur le parasite de pied de madura," Ann. de Vlnst. Pasteur, 1894), it is very 
probable that the disease occurring in India, known as madura=foot or mycetoma, is 
due to a polymorphous fission-fungus closely related to actinomyces, and called by 
Vincent the Streptothrix maduroB. The disease consists in a gradual swelling of one ex- 
tremity due to the formation of nodular deposits, which through softening become 
changed into abscesses and fistulous tracts, that upon pressure discharge pecu- 
liar brown or black, fish-roe, or truffle-like granules. Kanthack regards the fungus 
which is contained in the granules as identical with actinomyces; but the investiga- 
tions of Vincent and Boyce do not support this view. According to Boyce the strepto- 
thrix madurse occurs in two varieties, one white with fine dichotomously branching 
threads, the other black with branching pigmented threads. JJnna and Belhanco 
("Anatomic des indischen Madurafusses," Monh.f. prakt. Berm., 1900) also distinguish 
different forms of ray-fungi. The parasite of the madura disease has been known since 
1874 {Garter, "Mycetoma or the Fungous Disease of India," London, 1874; Xems and 
Cunningham, "The Fungous Disease of India," Calcutta, 1875; Hirsch, Virchow's und 
Hirsch's Jahresber., 1875, 1876), and was formerly known as Chionyphe Garteri. 

Literature. 

{Actinomycosis. ) 

Abee: Drei Falle von Aktinomykose. Beitr. v. Ziegler, xxii., 1897. 

BeMa: Systemat. Stellung d. Aktinomyces. Cbl. f. Bakt., xxiii., 1898. 

Berestnew: Ueber Pseudoaktinomykose. Zeitschr. f. Hyg.,xxix., 1899. 

Bertha: Einige bemerkenswerthe Falle von Aktinomykose. AVien. med. Woch., 1888. 



656 



THE PATHOGENIC FISSION-FUNGI. 



Bollinger: Eine neue Pilzkrankheitbeim Rinde. Cbl. f. d. med. Wiss., 1877; Dent 

Zeitschr. f. Thiermed., iii., 1877; Miincli. med. Woch., 1887. 
Bostrom: Unters. liber die Aktinomykose des Menschen. Beitr. v. Ziegler, ix., 1890. 
Chiari: Darmaktinomykose. Prag. med. Woch., 1884. 
Firket: L'actinomycose. Revue de med., 1884. 

Gozzolino: Ein neues Fadenbacterium. Zeitschr. f. Hyg., xxxiii., 1900. 
Grill: Aktinomykose d. Magens u. d. Darms. Beitr. v. BruDS, xiii., 1895. 
Hesse: Ueber Aktinomykose. Deut. Zeitschr. f. Chir., 34 Bd., 1893. 
Hoche; Histogenese du nodule actinomycosique. Arch, de med. exp., 1899. 
Howard: Actinomycosis of Central Nervous System (Lit.). Jour. of. Med. Res., 1903. 
Hummel: Entstehung d. Aktinomykose durch Fremdkorper. Bietr. v. Bruns, xiii 
1895. 

Illicli: Beitr. z. Klinik d. Aktinomykose, Wien, 1892. 

Johne: Deut. Zeitschr. f. Thiermed., vii., 1881; Cbl. f. d. med. Wiss., 1882; Aktino- 
mykose im Samenstrang kastrirter Pferde. Fortschr. d. Med., iii., 1885. 

Israel, J.: Mykose des Menschen. Virch. Arch., 74, 78 Bd., and Cbl. f. d. med. 
Wiss., 1883; Klin. Beitr. z. Kenntniss d. Aktinomykose des Menschen, Berlin 
1885. 

Israel, O. : Kuitivirbarkeit d. x\ktinomyces. Virch. xirch., 95 Bd. ; Cbl. f. d. med. 
Wiss., 1886. 

Krause: Zur Kenntn. d. Aktinomyces. Cbl. f. Bakt., xxvi., 1899. 

Kruse: Systematik d, Streptotricheen in Fltigge. Die Mikroorganismen, ii., 1896. 

Lebert: Anat. path. I c, Atlas t. I pi., II., Fig. 16. 

Levy: Ueber die Aktinomycesgruppen. Cbl. f. Bakt. xxvi., 1899 (Lit.). 
Liebmann: L'Attinomj'ce dell' uomo. Arch, per le Sc. Med., xiv., 1890. 
Martin: Actinomycosis of the Brain. Journ. of Path., iii., 1894. 

Moosbrugger : Ueb. die Aktinomykose des Menschen. Beitr. v. Bruns, ii., Tiibingea, 
1886. 

vanNiessen; Aktinomyces-Reinkultur. Virch. Arch., 150 Bd., 1897. 
Partsch: Die Aktinomykose des Menschen. Samml. klin. Vortr., No. 306-7, 1888. 
Pawlowsky et Maksutoff: Phagocytose dans I'actinomycose. Ann. de I'lnst. Pas- 
teur, 1893. 

Perroncito: Inoculation d'actinomyces. Arch. ital. de biol., vii., 1886. 
Ponfick: Bresl. arztl. Zeitschr., 1879, 9 Mai; Berl. klin. Woch., 1879, p. 347; Die Akti- 
nomykose des Menschen, Berlin, 1882, 
Schlegel- Aktinomykose. Ergebn. d. allg Path., v., Wiesbaden, 1900. 
Schurmayer: Ueber Aktinomyces. Cbl. f. Bakt., xxvii., 1900. 

Virchow. Trichinosis u. Aktinomykosis bei Schweinen. Virch. Arch., 95 Bd., 1884. 
Wolff u. Israel, J.: Reinkultur des A. ii Uebertrag. auf Thiere. Virch. Arch., 126 
Bd., 1891. 

Wright: Madura Foot. Jour, of Exp. Med., 1898; Actinomycosis. Ref. Handb. of 
Med. Sc.. 2d ed., 1900. 

§ 173. In additlou to those already described there is a large number 
of bacilli pathogenic for animals which may also cause infection in 
man. The most important animal diseases caused by bacilli are sympto- 
matic anthrax, swine-erysipelas, swine-plague, cattle-plague, and chicken- 
cholera. 

The bacillus of blackleg or symptomatic anthrax (Bacterie du charhon sympto- 
matique) is a rod with rounded ends about 3-5 fi long and 0.5-0.6 broad, and some- 
times possessing independent motion. According to the investigations of Bollinger, 
Feser, Arloing, Cornemn, Thomas, and others it is constantly found in blackleg. 

Blackleg occurs particularly in young cattle and in lambs, and is usually fatal 
within two days. It is characterized anatomically by a tumor-like swelling of the skin 
due to the exudation of a bloody serous fluid attended by the formation of gas in the 
subcutaneous, intermuscular, and muscular connective tissue. The bacilli are found in 
the region of the exudation and gas-formation, as well as in the spleen and liver. They 
do not stain with Gram's method. 

According to Arloing, Cornemn, and Tlionias, the bacilli may be cultivated, in the 
absence of oxygen, in chicken-bouillon, to which a small amount of glycerin and sul 
phate of iron is added. Kitasato and Kitt cultivated them in guinea-pig bouillon, agar, 
and gelatin in tlie absence of oxj^gen. They grow best at from 36'^-38" C, and form 
spores in the middle or at the ends of the rods, whereby the latter become somewhat 
swollen. The addition of sugar and glycerin to the nutrient medium aids the growth. 



ANIMAL DISEASES DUE TO BACTERIA. 



657 



The inoculation of cattle and sheep with bacilli which are attenuated by heating pro- 
duces an immunity against virulent bacilli. Cattle, sheep, goats, rabbits, guinea-pigs, 
swine, dogs, cats, and chickens are susceptible to the bacilli of symptomatic anthrax ; 
black rats are immune ; horses and donkeys occupy an intermediate position. 

The inoculation of guinea-pigs with virulent material — for example, with the dried 
juice of the muscle of cattle dying of blackleg — leads very quickly to a rapidly spread- 
ing swelling at the point of inoculation, due to the infiltration of the tissues with a 
bloody cedema. The bacilli spread with remarkable rapidity in the tissues, particularly 
in the subcutaneous and intermuscular tissue, and penetrate also into the muscles. They 
cause severe lesions of the vessels, leading to haemorrhages and serous exudations, and 
after a time to an abundant emigration of leucocytes. The animals usually die on the 
second or third day after the swelling has spread over a portion of the body. The blood 
usually remains free from bacilli. Spores are not formed in the living body. 

Literature. 

Arloing, Cornevin et Thomas: Le Charbon symptomatique de boeuf, Paris, 1887. 
Hess: Der Rauschbrand. Thiermed. Vortr., 1888, No. 4. 
Kitasato: Der Rauschbrandbacillus. Zeitschr. f. Hyg., vi., 1889, viii., 1890. 
Kitt: Der Rauschbrand. Cbl. f. Bakt., i., 1887; Deut. Zeitschr. f. Thiermed., xiii., 
1887. 

Roger: Charbon symptomatique. Rev. demed., 1891. 

Rogowitsch: Wirkung der Rauschbrand bacillen, Beitr. v. Ziegler, iv., 1889, 

The bacillus of swine=erysipelas {Loffler, Lydtin, Schottelius, and Schiitz) is a 
bacillus from 0,6-1.8 // long. It may be cultivated in bouillon, meat-infusion-peptone- 
gelatin, blood-serum, and sour milk. 

In gelatin-plates it forms peculiar radiating and branched figures. In stab-cultures 
it grows out in white streaks from the stab-canal like the bristles of a test-tube brush. 
In cultures the bacilli may form pseudothreads. They sometimes enclose shining spher- 
ules which are regarded as spores. By means of pure cultures the disease may be re- 
produced in susceptible swine. House-mice and pigeons die within two to four days 
after inoculation, and their blood contains numerous bacilli. 

In rabbits, inoculation is followed by an erysipelas-like inflammation which termi- 
nates either in a fatal general infection or in healing. Guinea-pigs and chickens are 
immune. 

According to investigations by Pasteur and Thuillier, and confirmed by Schottelius 
and Schutz, the virulence of the bacilli for swine may be attenuated by progressive in- 
oculations in rabbits. Susceptible swine inoculated with this vaccine do not die after 
inoculation and become immune to fully virulent bacilli. 

Swine-erysipelas occurs particularly in young herds of highly-bred (English) hogs, 
while the common breeds are nearly or wholly immune. The disease is characterized 
by fever and the appearance of red spots, later becoming brown, upon the neck, chest, 
and belly. Intestinal haemorrhages occasionally occur. More than half of the infected 
animals die, usually within a few hours or within four days. The autopsy shows 
swelling and localized haemorrhages in the mucosa of the intestine, swelling and ulcer- 
ation of the follicles, particularly in the ileocaecal region, swelling of the mesenteric 
lymph-glands, and petechiae of the serous membranes. 

The bacilli are found in the blood as well as in the lymph-glands, muscles, spleen, 
and kidneys, where they also lie in the blood-vessels. The majority are free; some are 
enclosed in leucocytes. They are stained by Gram's method. 

Literature. 

Hess: Der Stabchenrothlauf u. die Schweineseuche. Thiermed. Vortr., i., 1888. 
Kitt: Der Stabchenrothlauf der Schweine und dessen Schutzimpfung. Jahresb. d. 

Thierarzneisch. , Miinchen, 1885-86, Leipzig, 1887; Streptothrixform d. Bacillus. 

Cbl. f. Bakt., xxii., 1897, 
Loffler: Schweinerothlauf, Arb. a, d, K, Ges.-Amte, i., 1885. 
Lorenz: Schutzimpfung gegen Schweinerothlauf. Cbl. f. Bakt., xv., 1894. 
Lydtin und Schottelius: Der Rothlauf der Schweine, Wiesbaden, 1885. 
Schiitz- Rothlauf d. Schweine. Arb. a. d. K. Ges.-Amte, i., 1885. 

The bacillus of swine=plague is a small bacillus with rounded ends, 1-1,5 [i long, 
staining chiefly at its ends. It resembles the bacillus of chicken-cholera, and may be 
cultivated upon various media. It is regarded as the cause of the disease known in 



658 



THE PATHOGENIC FISSION-FUNGI. 



Germany as " Scliweineseuclie " or Schweinepest, in England as hog-cliolera or mcine-fever, in 
America as swine-plague and liog-cholera, and in Sweden and Denmark as swine-plague ; 
but it is not yet definitely determined Mdiether the swine-diseases of difTereot lands (with 
the exception of swine-erysipelas) are identical (see Preisz and Karlinski). 

The anatomical changes in swine plague vary with the locaHzation of the infection. 
In the lungs there are found multiple areas of necrotic and hremorrhagic pneumonia, 
and pleuritis. Intestinal infection leads to luemorrhagic and diphtheritic enteritis and 
(ill chronic cases) to caseous inflammations, which are accompanied by corresponding 
changes in the mesenteric glands, and occasionally also by peritonitis. The bacilli, 
besides being fovmd in the infected areas, are present in large numbers in the blood in 
acute cases. Hogs, guinea-pigs, rabbits, and mice are susceptible to inoculations. 

Literature. 

Bleisch und Fiedler: Scliweineseuclie. Zeitschr. f. Hyg., vi., 1889. 
Friedberger und Frohner : Pathol, der Hausthiere, 1896. 

Froscli: Ursachen der americanischen Scliweineseuche. Zeitschr. f. Hyg., ix., 1890. 
Marek: Histologic der Schweineseuclie. Zeitschr. f. Tliiermed., i., 1897. 
Preiz: Schweinepest und Schweineseptikamie. Zeitschr. f. Thiermed., ii., Jena, 1898. 
K/accug'lia: Bakt. d. amerikan. Schweineplague und der deutschen Schweineseuche. 

Cbl. f. Bakt., viii., 1890. 
Salmon, Billings, Smith: Jahresb. v. Baumgarten, 1886-95. 
Schiitz: Schweineseuche. Art. a. d, k. Ges.-Amte, i., 1886. 
Selander: Swinpest. Ann. de I'lnst. Pasteur, iv. 

Silbersch.midt : Swineplague, Hog cholera, Pneumoenteritis des pores. Ann. do 
I'Inst. Past., 1895. 

Smith: The Hog-Cholera Group of Bacteria. Cbl f. Bakt., xvi , 1894, p. 231. 

The bacillus of chicken=cholera, or avian typhoid, a disease occurring epidem- 
ically among chickens, is a small bacillus from 1-1.2 fx long, often somewhat constricted 
in its middle. It was first studied by Perroncito, then by Toussaint, Pasteur, Rimlta, 
Marchiafava, Celli, and Kitt. The disease is characterized clinically by great exhaus- 
tion and stupor, occasionally also by diarrhoeal intestinal discharges; anatomically by 
swellings of the liver and spleen, hoemorrhages and inflammations of the intestine, and 
also frequentl}' by pleuritis and pericarditis. 

The bacilii are found in the blood and therefore also in the capillaries of the differ- 
ent tissues. They may be cultivated upon nutrient gelatin, blood serum, and neutral- 
ized bouillon, as well as upon potatoes. They form white colonies. Feeding or inocu- 
lation of the bacilli causes in chickens a typical chicken-cholera ; pigeons, sparrows, 
pheasants, rabbits, and mice are also susceptible to the bacilli. In sheep, horses, and 
guinea-pigs they produce abscesses at the point of inoculation. 

Literature. 

Gamaleia: Aetiologie der Hiilmercholera. Cbl. f. Bakt., iv., 1888. 

Kitt: Gefliigelcholera. Cbl. f. Bakt., i., 1887; Deut. Zeitschr. f. Thiermed., xiii., 1888. 

Pasteur: Compt. rend., xc, 1880. 

"Wertheim: Cholera gallinarum. a. f. exp. Path., 26 Bd., 1889. 
Ziirn : Die Krankheiten des Hausgefliigels, Weimar, 1882. 

According to the view of Voges ("Krit. Studien u. exper. Untersuch. liber die Bakt. 
d. hamorrhag Septikamie und die durch sie bewirkten Krankheitsforraen, " Zeitschr. f. 
Hyg., xxiii., 1896, xxviii., 1898) the German sioine-plague, rabbit-septiccemia,'''' Wildseuche,'^ 
" Bi'iffelseuche, " chicken- and duck-cholera, American hog-cholera, swine-fever and " Frett- 
clienseuche,''^ are all caused by the same disease-agent — the bacterium of haemorrhagic 
septicsemia — and represent one and the same disease, to which he and Hueppe give the 
name of haemorrhagic septiccBmia. Preisz ("Schweinepest und Schweineseptikamie," 
Zeitschr. f. Thiermed., ii., Jena, 1898) distinguishes between Schweinepest Q,n6.^ Schweine- 
septikamie as two different diseases caused by different bacilli. Septicaemia may be 
associated with swine-plague as a secondary infection. Swine-plague is characterized 
by caseous plaques and ulcerations in the intestine, enlarged and in part necrotic lymph- 
glands of the abdominal and inguinal regions, and necrotic infiltrations of the skin and 
kidneys; septicaemia, on the other hand, according to Preisz, by a haemorrhagic pneu- 
monia, haemorrhagic fibrinous pleuritis and pericarditis, and haemorrhages froni the kid- 
neys. Karlinski ("Schweinepest und Schweineseuche," Zeit. f. Hyg.. xxviii., 1898) 



THE SPIRILLA. 



659 



expresses himself in a similar inannei' and also distinguisJies between ScTiweinepest and 
Schvuei nese uclie. 

The Bacillus diphtherise columbarum is a small, slender bacillus, which was 
isolated by Loftier ("Mi ttheil. a. d. k. Ges.-Amte," ii.) from the exudate of a pigeon 
dying of diphtheria, and is regarded {Babes and Pascarin, " Unters. liber die Diphtheric 
der Tauben," j?e^7s(•Ar. /. liyg., viii., 1890) as the probable cause of pigeon-diphtheria, 
a disease resembling human diphtheria. Loftier was able to reproduce the disease in 
pigeons but not in chickens by means of inoculations of pure cultures of the bacilli. 
Mice died in about five days after inoculation, and the bacilli were found in the blood- 
vessels of all the organs. 

According to Loffler (I. c.) a haciilus is also present in the diphtheria of calves, but 
he was not able to cultivate it pure or to determine its pathogenic significance. 

The diphtheria of calves and chickens is etiologically different from human dixph- 
ViiQriai {Esse r, " 1st die Diphtheric des Menschen auf Kalber iibertragbar, " Fortschr. d. 
Med., vi., p. 324; Loffler, "Mittheil. a. d. k. Ges.-Amte.." 1884; Putz, Fortschritte d. Med., 
v., p. 187). 

Besides the above, there are man}^ other bacilli which have been described as the 
cause of disease in animals. Thus, for example, according to Hoflich ("Die Pye- 
lonephritis bacillosa des Rindes," Monatsh. f. prakt. Thierheilk., ref. Centralb. f. 
Bakt., X.) and Enderlen, ("Primare infectiose Pyelonephritis beim Rinde," Deutsch. 
Zeitschr. f. Thiermed., xvii., 1891, ref. Cent. f. Bakt., x.), the frequently occurring 
pyelonepkritis of cattle is caused by a haciilus. Likewise, according to iVocar^^ (" Note 
sur la maladie des boeufs de la Guadeloupe connue sous le nom de Farcin," Ann. de 
V In. Past., ii., 1888) the worm disease of the ox, which was formerly of frequent occur- 
rence in France; and according to Oreste and Armanni (" Studii e ricerche intorno al 
barbone dei bufali," ref. Cent./. Bakt., ii., 1887) and wn Batz ("Die Barbonekrank- 
lieit," Deutsch. Zeitschr. f. Thiermed., xxii., 1896), the plague occurring among the Ital- 
ian buffalo know^n as harhone dei hufali is due to a bacillus (by Voges regarded as the 
bacillus of haemorrhagic septicaemia). According to Nocard and Boux ("Le microbe de 
la peripneumonie," Ann. de Vlnst. Past., 1898) the lung-plague of cattle is caused by 
an extremely small, motile bacillus, whose form is with difficulty determined. Accord- 
ing to BangC' Aetiologie des seuchenhaften Verwerfens," Zeitschr. f. Thiermed., i., 1887) 
bacilli should be regarded as the cause of the epidemic abortion of cows. Siegel and 
Busenius (" Krankheitserreger derMundund Klauenseuche, " Deutsch. mea. Woch., 1897) 
have described a bacillus as the cause of foot-and-mouth disease; but according to C. 
Frdnkel ("Der Siegelsche Bacillus," Hygien. Rundschau, vii., 1897) its pathological 
significance remains to be proved. Whether the microorganism described by Babes and 
Proca ("Aetiologie der Maul und Klauensueuche," Centralb. f. Bakt., xxi., 1897) is the 
cahse of foot-and-mouth disease is likewise still to be determined. Loffler and Frosch 
{Gbl.f. Bakt., xxiii., 1898, p. 371) are of the opinion that the nature of the infecting 
agent in foot-and-mouth disease has not yet been determined. Lundgim Die Renn- 
thierpest," Zeitschr. f. Thiermed., ii., 1898) found a bacillus similar to the bacillus of 
symptomatic anthrax, and pathogenic for mice and guinea-pigs, in an epidemic disease 
affecting the reindeer herds of the Laplanders in northern Sweden. 



3. The Spirt axd the Diseases C aused by Them. 
{a) General Bemarls upon the Spirilla. 

§ 174. The Spirilla, or Spirillacese, or Spirobacteria are divided iuto 
two genera, one of them called Spirillum, the other Spiroehcete. Many 
writers recognize still another genus, Vibrio. 

The genus Spirillum is characterized by the formation of short, stiff, 
shallow spirals, which in i^art possess flagella and show an active swarm- 
ing movement. The wavy rods are also called vibriones by many 
writers. 

Spirillum sive Yihrio rugula (Fig. 500, b) forms rods, from 6-16/^- long 
and 0.5-2.5 // broad, simply bent or having a shallow turn, and moves by 
means of llagella. It occurs in swamp -water, faeces, and in the slime 
from the teeth. 

Spirillum sive Vibrio serpens forms thin threads from 11-28 // long, 
having three to four wavy turns, and is found in stagnating fluids. 



660 



THE P^^THOGENIC FISSION-FUNGI. 



SpirUhim tenue lia.s very thin threads about 3-15 ,a long, having 2-5 
screw-like turns. 

Spirillum undida (Fig. 500, a) consists of a thread from 1-1. 5, a broad 
and 8-12 ,a long, having from one and a half to three turns, and furnished 
with a flagellum at one end. It occurs in various decomposing fluids and 
executes rapid twisting and darting movements. 

Spirillum volutans possesses threads 1.5-2/x 
thick and 25-30 m long, with two and a half to 
three and a half turns, and bearing a flagellum at 
each end. 

The genus Spiroch^ete (Fig. 501; is character- 
ized by long, flexible, closeh'-turned spirals. 

The Spirochcete plicatilis forms long, very fine, 
closely wound threads, from 100-225 ij. long ; it is 
of frequent occurrence in swamp -water and in 
gutters, and makes very rapid movements. 

Spirochsete buccalis sive denticola is 10-20 {j. 
long, pointed at both ends, and is not infrequent- 
ly observed in the secretions of the mouth and nose (cf. Fig. 187). It 
appears to possess no pathogenic significance. 

The spirilla, so far as they are not pathogenic, have been but little 
studied. They are present in large numbers in the contents of privy - 
vaults. According to Prazmowski Spirillum rugula causes decomposi- 
tion of cellulose, and forms terminal spores. According to Weibel a 
vibrio iDresent in nasal slime presents many forms of growth. Esmarch 
succeeded in cultivating a spirillum, called by him Spirillum ruhrum, upon 
the various ordinary media. In bouillon it forms spirals of from forty - 
three to fifty turns. Short spirilla execute li^'ely movements, but long 
ones, on the contrary, slow movements or are motionless. The colonies 
in firm nutrient media are at the beginning pale, but in time the portions 
not exposed to the air take on a wine-red color. In the spirilla of old 
cultures there appear three to four clear, dull-glistening spots that do 
not stain, and are probably to be regarded as spores. Cultures which 
contain such spirilla are more resistant to drying than others, but they are, 
however, very easily killed by heat. 

The long spirals may break up into short segments which possess only 
about three-quarters of a turn, but these may again grow in length, and 
undergo division. 

Kitasato and Kutscher have also succeeded in cultivating spirilla. 

Literature. 

{Life-history of the Spirilla.) 

Esmarch: Ueber die Reinkultiir eines Spirillum. Cbl. f. Bakt., i., 1887. 
Kitasato: Reinkultiir eines Spirillum aus faulendem Blute. Cbl. f. Bakt., iii,, 1888. 
Kutscher: Yibrionen ii. Spirillenflora d. Dungerjaiiclie. Zeitschr. f. Hyg., xx., 189S; 

Spirillum Undula minus 11. majiis. Cbl. f. Bakt., xviii.. 1895. 
Prazmowsky: ITnters. lib. die Entwickelunsso'escliicte einio-er Bakterien. Leipziar, 

1888. 

Salomon: Spirillum d. Saugethiermagens. Cbl. f. Bakt., xix., 1896. 
Weibel: Untersuchun gen liber Yibrionen. Cbl. f. Bakt., ii., 1887, iv., 1888. 

(b) The Fathogenie Spirilla. 

§ 175. The Spirillum cholerse asiaticse, or the Vibrio cholerce, also 
called eomma-baeillus {Ixicille-virgule eholerigene). was discovered by E. 




Pig. ^.■-Spirillum or Vi- 
hrio regula (h) and Spii^il- 
lum uitdida (a), obtained 
from a cold infusion of finely 
ctiopped earth-worms. Dried 
preparation treated with gen- 
tian-violet. X 600. 



THE SPIRILLA. 



661 



The 

-2/. 



(ft 



Fig. 501.— C h o 1 e r a - 
spirilla from a pure cul- 
ture. Cover-glass prep- 
aration stained witti 
fuclisin. X 400. 



Koch iu 1884, and is regarded as the cause of Asiatic cholera, 
si^irilla (Fig. 501) form small, comma-like, curved rods from 0. 
long. 

Cultures of cholera-spirilla may be obtained upon a great variety of 
culture-media of a slightly alkaline reaction. The temperatures most 
favorable for their develoiDment lie between 25° and 
30° C. ; at between 16° and 8° C. they are stiU capable 
of a feeble development. 

On gelatin -plates they form round, flat, yellowish 
discs which liquefy the gelatin only slowly. At 
a low magnification the cultures are irregular in 
outline, and of a granular or furrowed and rough 
surface, appearing as if strewn with small par- 
ticles of glass (Koch). Through the liquefaction of 
the gelatin in its immediate neighborhood there is 
formed a funnel-shaped cavity, to the bottom of which the colony sinks. 

Stab -cultures in gelatin form on the second day a whitish cord corre- 
sponding to the line of the stab (Fig. 502), in the immediate neighbor- 
hood of which the gelatin is liquefied. The canal thus 
, - formed widens out above into a funnel part which is 

filled in its lower portion with liquefied gelatin and in 
its uj)per with air. The widening of the funnel of the 
canal of inoculation takes place very slowly, so that its 
edge reaches the wall of the tube only after five to six 
days. 

On potatoes at from 30°-35° C. the spirilla form 
light-brown cultures, on agar-agar grayish-yellow slimy 
cultures. They grow also in bouillon, blood-serum, and 
milk. 

They do not increase in pure water (Bolton), but 
do so in water contaminated with substances furnishing 
nutrient material. 

The cholera-spirilla are aerobic, but they are also 
able to grow under anaerobic conditions. According to 
investigations by Hueppe cultivation with a deficient 
supply of oxygen increases the virulence of the culture ; 
but the resisting power against injurious agents — for 
example, against acids — is on the other hand lowered ; 
with free access of oxygen the reverse takes place. 
Pfeifi'er, however, found that young cultures grown in 
the presence of oxygen also contained poison. The 
spirilla present in fresh dejections (Hueppe) are easily 
killed, and have but little infecting power ; whereas the 
growth of the spirilla outside of the body increases their 
resistance (for example, against the gastric juice) and 
makes them at the same time more capable of causing 
infection in new individuals. They are easily destroyed 
by desiccation in free air (Guy on) and by high temper- 
atures, and by boiling for a short time. They are easily 
supj)lanted by saprophytic bacteria when the nutrient 
material and the temperature are not suitable. In the 
contents of privy- vaults they soon die out (Koch) . They 
FIG. 503.-stab-cui- are very easily killed by acids, mercuric chloride, and 
chSera^spSiifa.^^' carbolic acid. According to observations by Koch they 




662 



THE PATHOGENIC FISSION-FUNGI. 



may live in well water for thirty days, in sewage for seven days, and on 
damp linen for three to fonr days. Nicati and Eeitsch found them alive 
after eighty- one days in water taken from the harbor of Marseilles. 

In cultures thej^ sometimes form short rods, more or less curved (Fig. 
501) and often joined in pairs; at other times they form long spirals. 
With these there also occur straight rods, and occasionally the majority 
form rods which show the curve only imperfectly or not at all. In 
fluid media to which oxygen has access they show active movements, 
which may be easily observed in hanging drops. According to investi- 
gations by Loffler the motility is dependent upon a terminal flagellum. 

At a certain degree of exhaustion of the food-material there frequently 
appear involution-forms, in which the rods are sometimes shrunken, 
sometimes swollen, thus creating a great variety of forms. A globular 
swelling, as well as the formation of spots which do not take the stain in 
stained preparations, occur as the result of degeneration, and have often 
been erroneously interpreted as phenomena of fructification. Spore- 
formation has not been demonstrated. The addition of hydrochloric or 
sulphuric acid to cultures of cholera-spirilla in peptone -containing 
media (peptone -meat -infusion or an alkaline, one-per-cent. solution of 
peptone containing one per cent, of salt) causes the culture to assume 
a rose-red or Burgundy-red color, due to the formation of a coloring- 
matter, cholera-red. According to Salkowski, this is a nitroso-indol 
reaction. 

When gaining entrance to the intestinal tract of man the spirilla, in so 
far as they are not destroyed by the action of the gastric juice or their 
growth otherwise prevented, develop both in the small and large intes- 
tines, and their multiplication is followed by a marked transudation from 
the intestinal mucosa, so that the intestine becomes filled with a fluid re- 
sembling meal-soup or rice-water, in which flakes of descxuamated epi- 
thelium which has undergone mucoid degeneration float about. 

The spirilla are always present in great numbers in the intestinal con- 
tents, and are found in the lumina of the intestinal glands, whence they 
may penetrate between and beneath the epithelial cells. 

In recent cases the spirilla may usually be demonstrated in cover-glass 
preparations stained with methylene -blue or fuchsin. Fresh dejecta, as 
well as soiled linen, are suitable for the examination, since, according to 
observations made by Koch, the spirilla may multiply actively for some 
time uiDon moist linen and moist earth. In old cases the demonstration 
of the spirilla is more difficult but nevertheless succeeds in all cases, and 
is attainable most surelj" by means of plate -cultures. In order to facili- 
tate the separation of cholera-spirilla from other intestinal bacteria, 
Schottelius recommends the mixing of the dejecta with double the 
amount of a slightly alkaline meat -infusion, and allowing the mixture to 
remain uncovered for twelve hours at a temperature of from 30^-40° C. 
The spirilla requiring oxygen will develop i^articularly ui)on the surface, 
and may be easily transferred thence to plate-cultures. Koch recom- 
mends for this purpose a solution of peptone with common salt. 

The presence of cliolera- spirilla in the intestine excites an inflammation, 
which in the beginning finds expression in redness, swelling, marked 
transudation, mucoid degeneration of the epithelium, and desquamation ; 
later, by hsemorrhages, formation of sloughs, and ulceration. It is char- 
acterized constantly by a more or less marked cellular infiltration of the 
tissues. The solitary follicles and Peyer's patches are swollen even in 
fresh cases. Death may take place after a few hours or after one to 



ASIATIC CHOLERA. 



668 



three days. If the disease lasts a longer time, the intestinal contents 
become more consistent and the intestinal mucosa shows ulcerative 
changes. 

According to our present knowledge, the spirilla produce poisonous 
substances which cause local damage to the mucosa of the intestinal 
canal, and when absorbed give rise to symptoms of intoxication and 
cause paralysis of the vessels. Small foci of degeneration are often pres- 
ent in the liver and kidneys, within which the gland-cells show cloudy, 
fatty, or hyaline degeneration, or are necrotic. Moreover, the kidneys 
may frequently show cloudiness caused by a toxic degeneration of the 
epithelium ; occasionally also a swelling of the cortex. Ecchymoses in 
the epicardium are of frequent occurrence, and in the later stages patches 
of necrosis may also occur in the mucous membrane of the vagina. The 
long-continued presence of spirilla in the intestine may give rise to ulcer- 
ation. Finally, the spirilla may be crowded out by the putrefactive bac- 
teria present in the intestine, and ultimately die out. Through the 
absorption of the products of decomposition a new intoxication may 
arise, which is not dependent upon the original spirilla. 

According to Koch, Nicati, and Rietsch, cholera-spirilla may also be 
found in the vomitus. Mcati, Rietsch, Tizzoni, and Cattani found them 
also in the ductus choledochus and in the gall-bladder. According to 
the statements of these authors the spirilla usually do not enter the 
blood, but in cases of severe infection they may be spread throughout 
the body. 

Koch demonstrated the presence of spirilla in a tank in India which 
furnished the inhabitants of the region with their entire supply of water 
for drinking and other purposes, at a time when a part of the inhabi- 
tants were sick and dying of cholera. Since then, they have often been 
demonstrated in water-supplies during cholera epidemics. 

According to investigations by Mcati, Rietsch, van Ermengem, and 
Koch, symptoms resembling cholera may be produced in experimental 
animals through the introduction of cholera-spirilla into the intestinal 
canal. This experiment succeeds when cultures are introduced directly 
into the duodenum or small intestine (^^^icati and Rietsch) ; as well as 
when the gastric juice of the animals (guinea-pigs) is neutralized with a 
five-per-cent. solution of soda, the bowels being quieted by an injection 
of 1 c.c. of tincture of opium to every 200 gm. of the body-weight, and 
one or more droiDS of a pure culture of the spirilla then introduced into 
the stomach (Koch). 

The animals thus inoculated die with marked symptoms of collapse. 
The small intestine is found to be filled with a watery, flocculent, color- 
less fluid containing spirilla in great numbers ; the intestinal mucosa is 
reddened and swollen. 

Asiatic cholera is endemic in Lower Bengal and never entirely disap- 
pears there. Thence it spreads at times throughout India, and is carried 
by transportation over a larger or smaller part of the world. Since the 
spirilla are easily killed outside of the body the transportation must be 
effected mainly by individuals suffering from the disease. The infection 
probably occurs exclusively through the alimentary tract, as the re- 
sult of the introduction of infected beverages, food, or some other sub- 
stance into the mouth; but without doubt not every introduction of 
cholera-spirilla into the intestinal canal is followed by infection. 

Moreover, it not infrequently happens that the spirilla increase in the 
intestine, but excite only slight changes, so that the infected individual 



664 



THE PATHOGEXIC FISSIOX-FUNGI. 



suffers no marked symptoms, and tlie diagnosis can only be made through 
the demonstration of spirilla in the stools. 

If the cholera-spirilla get into the water-supply and there increase, 
cholera may develop in the given region with very great rapidity. If, 
on the contrary, the infection takes place l)y direct or indirect contagion 
from man to man, the spread is slow, in that the disease is confined to 
those who come into contact with the sick, or with articles contaminated 
by the latter. The incubation period is from one to two days. 

lu the intestines of convalescents the spirilla, according to im'estiga- 
tions of Kolle, may lixe for a long time and multiply without giving rise 
to any symptoms betraying their presence. Kolle was able to demon- 
strate them in a number of cases after five to eighteen days, and in indi- 
vidual cases as long as twenty to forty-eight days. 

One attack of cholera makes the individual immune for a certain 
time. The immunity depends upon the presence of bactericidal anti- 
bodies. Through these bodies the organism may be i^rotected from 
cholera ; but in those who have already contracted the disease the protec- 
tive influence is of no avail (cf. § 32). 

The poison wliich is produced by the cholera-bacillus and wliich causes the essen- 
tial clinical symptoms of a cholera-infection is not known. Gamale'ia believes that it 
is a nucleo-albumin ; SdioJl that it is a peptone (choleratoxopepton). Ffeifftr is of the 
opinion that it is an element of the cell-body. According to Metsclinucoff and others it 
is secreted by the cells. Emmericli and Tsuhoi would refer the morbid symptoms of 
cholera to a nitrite poisoning, since nitrites in small doses cause retching, vomiting, dis 
charge of thin-gruel faeces, fall of temperature, heart failure, cyanosis, and cramps of 
the extremities and muscles of the neck — that is, symptoms resembling those of cholera 
— and, moreover, because the cholera-spirilla are able to form nitrites out of nitrates 
(contained in the food). 

The virulence of cholern-rultures dijf\rs greatly, according to the place of origin and 
the age. The virulence decreases with the age. Guinea-pigs which are ver}- suscep- 
tible to intraperitoneal inoculations of cholera may be protected against this infection 
by the intraperitoneal injection of attenuated cultures; but no absolute immunity can 
be produced in this way. The blood-serum of human individuals that have recovered 
from an attack of cholera shows protective properties for guinea-pigs for several weeks 
after the attack. 

The uitroso-indol reaction in cultures of the cholera-spirilla is due to the fact that 
the cholera-spirillum in peptone solutions not onl}' forms indol but also nitrites. The 
addition of hydrochloric or sulphuric acid sets free niti'on> acid Avhich forms a red color 
with indol. 'With the SpiriUirin nf FinJder, the SpiriUiim nf Metschnikoff, and the Spir- 
illiim of Beneke. which also produce indol. the red color of the cultures occurs only when 
potassium nitrite is added with sulphuric acid, or when nitrous acid alone is added. 

Spirilla Reserahling the Cliolera-Spirilhim. 

(1) The Spirillurn of Finidtr and Prior, found l\v these observers in the dejecta of 
persons suffering from cholera-nostras, after the discharges have stood for some time in 
a vessel. The spirilla are very similar to the cholera-spirilla, only somewhat longer and 
thicker. In plate-cuUures they are distinguished from the latter only in the fact that 
the small colonies are not distinctly granular and have a sharp contour. Gelatin is 
quickly, not slowly, liquetied: and consequently in stab-cultures after twenty-four 
hours a sac-like tube filled with cloudy fluid (Fig. 503) is formed, which soon reaches 
the wails of the tube. 

On potatoes (FU'ffpe). even at room temperatures, they form within forty-eight 
hours a grayish-j^ellow, slimy coating, sharply marked oft' from the substance of the 
potato by a whitish border; while cholera-spirilla do not grow at all at room-temper- 
ature, and at higher temperatures form brown coatings. 

Further, they cause a foul-smelling decomposition : and are rather resistant to dry- 
ing. When introduced into the intestine of guinea-pigs by the method given above, 
they produce effects similar to those caused by cholera-spirilla, but less intense. 

^It is very doubtful whether the >/'// /////,'/ of FinJder and Prior possesses a patho- 
genic significance for cholera-nostras. since the dejecta from which these investigators 



ASIATIC CHOLERA. 



665 




obtained their cultures were not fresh ; and other authors have failed to find the spirilla 
in corresponding cases ( KartuUs, " Zur Aetiologie der Cholera nostras, " Zeitschr. f. 
Hyg., vi., 1889). Knisl {Milnchemr drztliches Intelligenzhlatt, 1885), 
on the other hand, found them in the Cfecal contents of a suicide, 

(2) Spirillum tyrogenum, found in cheese by Deneke in Fliigge's 
Institute {Deut. med. Wochenschr., 1885), is also very much like the 
cholera-spirillum, but is somewhat smaller, and the long spiral 
threads are more closely wound. Cultures on gelatin-plates form at 
first sharply contoured discs that by low magnification appear dark, 
and liquefy the gelatin more rapidly than the spirillum of Koch. 
In stab-cultures they behave like the Finkler-Prior spirillum, but do 
not grow upon potato. 

(3) Spirillum sputigenum is a spirillum of the shape of a curved 
rod, somewhat longer and thinner than the cholera-spirillum. It 
occurs in the saliva, and cannot be cultivated upon the ordinary 
media. 

(4) Vibrio of Metschnikoff {Gamaleia, "Vibrio Metschnikovi et 
ses rapports avec le microbe du cholera asiatique," Annal. d. Vlnst. 
Past., ii,, 1888; iii., 1889; Pfeiffer, "Ueber den Vibrio Metschnikovi 
wind sein Verhaltniss zur Cholera asiatica," Zeitschr. f. Hyg., 1889) 
is a fission -fuDgus isolated by Gamalei'a in an epidemic occurring 
in chickens in Odessa, which was characterized by diarrhoea and 
enteritis. When cultivated it shows a very great resemblance to 
tiie cholera-spirillum of Koch, The spirillum is most easily ob- 
tained pure by inoculating pigeons with the blood of diseased 
<diickens. The pigeons die in from twelve to twenty hours and 
s&ow the spirilla in the blood and in the intestinal tract. 

Literature. 

{Spirillum of Asiatic Cholera. ) 
Barth: Die Cholera, Breslau, 1893. 

Brieger: Choleraroth. Deut. med. Woch., 1887; Stoffwechsel- 

producte d, Cholerabacilleu. Berl, klin. Woch., 1887. 
Bujwid: Chem. Reaction f. d. Cholerabakt. Zeitschr. f, Hyg., ii., 

1887; Cbl. f, Bakt., iii., 1888. 
Dieudonne : Uebersicht iiber die choleraahnlichen Vibrionen. Cbl. 

f. Bakt., xvi., 1894, 
Dunbar: Ditferentialdiagnose zw, Clioleravibr. u. and. Vibr, 

Zeitschr. f. Hyg., xxi., 1896. 
Emmerich u. Tsuboi: Die Cholera, eine durcli die Cholerabacilleu 

verursachte Nitritvergiftung. Miinch. med. Woch., 1893. 
van Ermengem: Rech, sur le microbe du cholera asiatique, Bruxelles, 1885; Neue 

Untersuchungen uber Choleramikroben, Wien, 1886. 
Finkler u. Prior : Deut. med, Woch., 1884; Forschungen lib. Cholerabakterien, Bonn, 

1886. 

Fliig'g'e: Verbreitungsweise u. Verhiitung d. Cholera. Zeitschr. f. Hyg,, xiv., 1893. 
Praenkel: Choleraleichenbefunde. Deut, med, Woch., 1893. 

Galeotti: Immunitatu. Bakteriotherapie gegen Cholera. Cbl. f. allg. Path., 1895 (Lit,), 
Gamaleia: Rech. exper, sur les poisons du cholera. Arch, de med. exp., iv., 1892. 
Cruyon: Influence de desiccation sur le bac. du cholera. Arch, de med. exp., 1893. 
Hesse: Nahrungsmittel als Nahrboden f. Typhus u. Cholera. Zeitschr. f. Hyg., v,, 
1889. 

Hueppe: Dauerformen d. Cholerabacilleu, Fortschr. d, Med., iii., 1885; Giftigkeit d, 

Cholerabakterien. Deut, med, Woch,, 1889; Aetiologie d. Cholera. Bsrl. klin. 

Woch., 1890; Aetiol. u, Toxikol, d. Cholera. Deut. med. Woch., 1891; Die Chol- 

eraepidemie in Hamburg, 1892, Berlin, 1893. 
Kitasato: Widerstandsfahigkeit d. Cholerabakterien gegen Eintrocknen u, Hitze. 

Zeitschr. f, Hyg,, v., vi. ; Verbal ten d, Cholerabakterien im menschl, Koth u, in 

Milch, lb., v., 1889, 

Koch.: Aetiologie d. Cholera. Deut. Vierteljahrsschr. f. off. Gesundheitspflege, xvi., 
1884; Conferenz z, Erorterung der Cholerafrage. Deut. med, Woch,, 1884-86; 
Choleradiagnose. Zeitschr, f. Hyg,, xiv,, 1893; Die Cholera in Deutschland wah- 
rend des Winters, 1892-93. lb., xv., 1893. 



Fig. 503. — Stab- 
culture, in g'elatin, 
of the Spirillum of 
Finkler and Prior. 



666 



THE PATHOGENIC FISSION-FUNGI. 



Koch 11. Gaffky: Bericlit liber die Thatigkeit dcr z. Erforscliuiig d. Cholera im J., 
188), nach Aegypten u. Indien entsaridten Commission. Arb. a. d. K. G.-A., iii., 

i88r. 

Kolle: Ueber dieDauer des Yorkommens von Clioleravibrionen in den Dejectioneu von 

Cholerareconvalescenien. Zeitschr. f. Hyg., xviii., 1894. 
Lehmann: Die modernen Clioleratlieorieen. Biol. Centralbl., v., 1885. 
Lustig-; Bakteriolog. Stiidien liber Cholera asiatica. Zeitschr. f. Hyg., iii., 1888. 
Metsclinikoff: Toxine et antitoxine cholerique. Ann. de I'Inst. Pasteur, 1896. 
Jfeuhaus: Ueber die Geisseln an den Bacillen der asiat. Cholera. Cbl. f. Bakt., v., 

1889. 

Nicati et Rietscli: Rech. sur le cholera, Paris, 1886. 

V. Pettenkofer : Stand der Cholerafrage. Arch. f. Hyg., v., vi., vii., 1887; Der epi- 
demiologische Theil des Berichtes liber die Thatigkeit der zur Erforschung der 
Cholera im Jahre 1883 nach Aegypten imd Indien entsandten Commission. Mlinchen 
u. Leipzig, 1888; Ueber Cholera. Mllnch. med. Woch., 1892. Cbl. f. Bakt., xii., 
1892. 

Pfeiffer: Choleragift. Zeitschr. f. Hva:., xi., 1892; Antikorper d. Cholera. lb., xx., 
1895. 

Riedel : Die Cholera, Entstehimg, Wesen u. Verhlitimg derselben, Berlin, 1887. 
Rumpf : Die Cholera asiatica u. nostras, Jena, 1898. 

Rumpf u. Gaffky: Die Cholera. Verb. d. XIT. Congr. f. inn. Med., Wiesbaden, 1893. 
Salkowski: Ueber das Choleraroth. Virch. Arch., liO Bd., 1887. 
Santa Sirena ; Sulla resistenza del bacillo virgolo di Koch nelle acque. Rif. Med., 
1890. 

Scholl: Unters. liber giftige Eiweisskorper bei Cholera. Arch. f. Hyg.. xv., 1892. 
Schottelius: jSTachweis der Cholerabac. in den Dejectionen. Deut. med. Woch., 1885, 
1889. 

Schucliardt; Ueber das Choleraroth. Virch. Arch., 110 Bd., 1887. 
Sobernheim : Choleraimmunitat. Zeitschr. f. Hyg., xx., 1895. 
Stieda: Neue Arbeiten liber Cholera asiatica. Cbl. f. allg. Path., iv., 1893. 
Tizzoni et Cattani: Rech. sur le cholera asiatique. Beitr. v. Ziegler, iii., 1888. 
Tschistowitscli : Verand. d. Gehirns bei Cholera. Virch. Arch., 144 Bd., 1896. 
Voges: Die Choleraimmunitat. Cbl. f. Bakt., xix., 1896 (Lit.). 

Wassermann : Unters. lib. Immunitat gegeu Cholera asiatica. Zeitschr. f. Hvg., 
xiv., 1893. 

§ 176. The Spirochaete Obermeieri (Fig. 504) is found constautly in 
the blood of patients suffering from relapsing fever during the attacks 
of the fever, and the multiplication of these organisms in the body is the 
cause of the disease. 

The spirochaete is 16-40 long, and possesses numerous spiral turns. 
In a fresh drop of blood it shows very active motion. Carter and Koch 

succeeded in producing the disease in apes 
by inoculation with the spirochaete; but 
nothing definite is known of its mode of 
development and habitat outside of the 
blood. The whereabouts of the spirochtete 
or of its spores during the afebrile stages 
of the disease are not known. The subcu- 
taneous inoculation into apes of blood con- 
taining the spirochaete is followed only after 
several days by an attack of fever, and the 
spirochsete is found in the blood only during 
the febrile stage. According to the autopsy - 
findings observed in man, the spleen is swol- 
len and contains numerous yellow foci of degeneration, and often also 
anaemic infarcts. 

According to investigations by Mkiforoff' the histological examina- 
tion of the spleen shows extensive cell-necrosis and cell -degeneration 
(Fig. 505, c), as well as deposits of fibrin in the veins of the pulp, and 
proliferative processes in the pulp-cells. Further, numerous large pulp- 




FiG. bOi.—Spirochoete Ohermeieri 
from the blood of an individual ill 
with relapsing fever. After a dried 
preparation stained with methyl-vio- 
let. X 475. 



SPIRILLUM OF RELAPSING FEVER. 



667 



cells (/) enclose red and white blood-cells or the remains of such. Fi- 
nally, numerous spirilla are found, especially in regions which are not 




Fig. 505.— Portion of tissue and isolated cells from a splenic follicle with partial necrosis, in relapsing 
fever. ( After Nikiforofl. ) (Potassium bichromate and sublimate, methylene-blue.) a. Free spirilla : h, 
lymphocytes with spirilla ; c, non-nucleated lymphocytes ; d, large, e, small mononuclear pulp-cells : t\ 
phagocytes enclosing leucocytes and red blood-cells and their remains ; y, free red blood-cells. X about 6tHl. 

wholly necrosed but contain degenerated and necrotic cells, in part free 
(a), and in part enclosed in leucocytes (b), partly well-preserved, and 
partly beginning to show disintegration. 

The spirochsetes stain especially well, in cover-glass preparations, with 
alkaline methylene-blue and fuchsin. 

Literature. 

(Typhus Becurrens.) 

Cantacuzina : Sphilloses des oies. Ann. de I'lnst. Pasteur, 1899. 
Gabritschewsky : Ztir Pathol, d. Spirochaeteuinfection. Cbl. f. Bakt., xxvi., 1899. 
Heydenreich: Der Parasit des Riickfalltyphus, Berlin, 1877. 
HonI: Febris reciirrens. Ergebn. d. allg. Path., iii., 1897. 

Lubimofif: Patliolog.-anat. Veranderungen bel Typhtis biliosus. Virch. Arch., 98 Bd., 
1884. 

Metschnikoff: L^eb. den Phagocytenkampf bei Ruckfalltyphus. Virch. Arch., 109 
Bd., 1887. 

Nikiforoff; Zur path. Auat. u. Histol. d. Milz bei Recurrens. Beitr. v. Ziegler, xii., 
1892. 

Obermeier. Cbl. f. d. med. Wiss., 1873; Berl. klin. Woch., 1873, No. 33. 
Ponfick: Anat. Studien itber den Typhus recurrens. Virch. Arch., 60 Bd., 1874. 
Puschkareff: Zur pathol. Anatomieder Febris recurrens. Virch. Arch., 118 Bd., 1888 
Sudakewitsch : Rech. sur la lievre recurrente. Ann. de I'lnst. Pasteur, v., 1891. 



CHAPTER XI. 



The Yeasts and iloulds, and the Diseases Caused by 

Them. 

§ 177. The yeasts (Blastomycetes) and the moulds (Hyphomycetes) 

belong, as do the schizomycetes, to the non-chlorophyllaceous thallo- 
phytes. With the schizomycetes they have no phylogenetic relationship ; 
on the other hand, they are closely related to one another. 

The moulds and yeasts, like the schizomycetes, derive their nourish- 
ment from organic substances containing carbon. The majority find 
their food in dead organic substances, and belong therefore to the sapro- 
phytes ; some are able to obtain nourishment from living tissues, and are 
to be classed, at least at times, with the parasites. In human beings both 
forms occur. 

Outside the organism the moulds are generally known as the pro- 
ducers of the different mouldy films which so frequently develop upon 
organic substances. They belong to different groups of fungi. 

The yeast-fungi are the cause of alcoholic fermentation, and form the 
scum on the top of alcoholic beverages. 

Literature. 

{Moulds and Yeasts. ) 

De Bary, A. : Vergl. Morpliologie d. Biologie d. Pilze, Mycetozoen u. Bakterien, Leip- 
zig, 1884. 

Brefeid: Unters. aus dem Gesammtgebiete der Mykologie, Heft i.-x., Leipzig, 
1874-91. 

Gobel: GrimdzLige der Systematik ii. spec. Pflanzenmorphologie, Leipzig, 1883 
Janssens: Ueber den Kern der Hefezellen. Cbl. f. Bakt., xiii., 1893. 
Jorg-ensen: Die Mikroorganismen der Gaiirimgsindustrie, Berlin, 1892. 
Koch : Jaliresber. liber die Fortschritte der Lehre von den Gabrimgsorganismen, 1890- 
1900. 

liudwig: Lehrb. der niederen Kryptogamen, Stuttgart, 1892. 

Raum: Zur Morphologie u. Biologie der Sprosspilze. Zeitscbr. f. Hyg. , x , 1891. 

Sachs: Vorles. tiber Ptlanzenpbysiologie, Leipzig, 1882. 

Tavel: Vergleichende Morpbologie der Pilze, Jena, 1892. 

TJhlworm n. Hansen: Cbl. f. Bakt., II. Abth., Bd. 1-6, Jena, 1895-1900. 

Zopf: Die Pilze. Handb. d. Botanik v. Schenk, iv. 

§ 178. Yeasts occur in man in the form of nalted ot encapsulated, oval 
or round cells of varying size. They are found chiefly as harmless sapro= 
phytes, most frequently in the upper part of the intestinal canal — in the 
stomach — where they are almost constantly present; and when beverages 
in the process of alcoholic fermentation are taken they may occur in 
large numbers, and may also multiply. In the bladder they may like- 
wise multiply, in case the urine contains sugar : and may cause fermen- 
tation of the urine with evolution of carbonic-acid gas. 

As parasites no importance has been attached to them until .very 
recently, but the investigations of Busse, Buschke, Sanfelice, Curtis, and 

668 



THE PATHOGENIC MOULDS AND YEASTS. 



669 




Fig. 50Q.—Saccha- 
romyces ellipsoideus. 
X 400. 



others have established the fact that there are also species of Saccharo- 
mycetes of pathogenic importance. According to these observations the 
pathogenic yeasts can multiply in different tissues, in 
the skin, periosteum, lungs, and glandular organs, and 
can excite either purulent inflammations^ or proliferations 
of granulation tissue, which run a course similar to that 
of an infection with actinomycosis or tuberculosis. In 
inflammatory foci the yeast cells are for the chief part 
provided with a capsule. They may be present in large 
numbers so that through their mass alone they may give 
rise to tumor-like swellings. Through degenerative 
changes, crescentic forms may develop from the oval 
yeast -cells. 

In solutions containing sugar the blastomycetes form oval cells (Fig. 
506). Eeproduction takes place through budding and constriction ; on 

any portion of the parent cell there may 
develop an excrescence, which is constrict- 
ed off after it reaches the size of the mother 
cell. Under certain conditions the cells 
may grow out into threads, but in these 
threads no subsequent segmentation occurs ; 
jointed threads arise through budding 
( Cienkowsky , Grawitz ) . A dilute culture - 
medium favors the formation of threads. 

nould=fungi are found in man partly 
in the form of simple or branched, un- 
jointed or jointed threads of varying thick- 
ness; and partly as oblong or even as 
^ ^ <a - ^ spherical cells. The threads are desig- 

11 I "^^^^ hyphas (Figs. 507, 508), and the 

I /¥ / Si m'Si^^ which they form as mycelium ; the 

10 A ^ spherical or long oval or short cylindrical 

cells, which are frequently arranged in the 
form of a rosary, as spores, or better as 
conidia=spores (Figs. 507, 508). Only rare- 
ly nas there been observed within the body 
a fructification upon special fruit- organs. 
The moulds are partly saprophytes and partly parasites ; and are 
found almost exclusively in regions accessi- 
ble from without, as the skin, intestinal 
canal, respiratory tract, external ear, vagina, 
etc. Only exceptionally, and under especial 
conditions, do they reach the internal organs, 
as, for example, the brain. It is evident that, 
on the whole, the living tissues of the human 
not afford a suitable nutrient 
the mould-fungi, and the life- 
the tissue-cells for the greater 
permit their development and 
multiplication. The need for oxygen pre- 
vents the growth of moulds in many tissues ; 
and for many moulds the temperature of the 

body is too high. Moreover, the chemical composition of the tissues 
does not offer to the moulds a favorable mixture of nutrient material. 




Fig. 507.— Fresh favus-mass consist- 
ing of hyphae, conidia, and epithelial 
cells. (After Neumann.) 



organism do 
medium for 
activities of 
part do not 




Fig. 508.— From a deposit of aphthae, 
on the tongue of a man dying of ty- 
phoid fever. X 375. 



670 



THE PATHOGENIC MOULDS AND YEASTS. 



Moulds growing as saprophytes occur iu man most frequently in 
the alimentary canal, particularly in the mouth, pharynx, and (Esophagus. 
They develop in these regions particularly when the ingesta or desqua- 
mated cells lie undisturbed in one position for a long time, and when the 
function of the organ concerned is lowered. They are recognized through 
the formation of hyphte and conidia. 

In the external auditory canal moulds grow especially in abnormal 
masses which fill u^) the passage and consist in part of cerumen, or of 
inflammatory exudates and desquamated cells, and in part of substances 
introduced from without. 

In the lungs moulds are occasionally found upon the necrotic wall of 
cavities, particularly those due to tuberculosis, as well as in necrotic and 
gangrenous hsemorrhagic infarcts, etc. In the air-passages they are 
observed most frequently in bronchiectases. 

In the alimentary tract, as well as in the ear and lungs, the moulds 
form chiefly a whitish deposit on or in the tissues. In the event of fruc- 
tification upon especial fruit-bearers they may take on a brown, gray, or 
even black appearance. In the intestinal canal the food and drink may 
give them various colors. 

At first the moulds grow in dead material, but they may penetrate 
thence more or less extensively into living tissue ; and cases have been 
observed in which they have even entered the circulation and have been 




Fig. 509.— Section througrh an aphthse-covered oesophagus of a small child (alcohol, carmine. Gram's), 
a. Normal epithelium; Ik connective tissue; c, swollen and desquamated epithelium infiltrated with fun- 
gus-threads ; d, epitheUum infiltrated with cells e, cocci and bacilli ; f, cellular focus In the connective 
tissue. X 95. 



carried by the blood-stream to distant organs. Thus the fungous growth 
called thrush {aphthm, muguet), which appears chiefly upon the mucous 
membrane of the mouth, pharynx, and aesophagus, and more rarely upon 
that of the stomach, intestine, and vagina, and upon the nipples of nursing 
women, cannot be regarded as a pure saprophytic, but, on the contrary, 
is a parasitic growth, which penetrates into living epithelium (Fig. 
509, c), and even into the underlying connective tissue. It is true, how- 
ever, that thrush occurs chiefly in infants and in debilitated invalids 
who are no longer able to cleanse the moutli, throat, and oesophagus, so 
that some especial local predisposition appears to be necessary for its 
development, and it is probable that the primary colonization of the 
fungus takes place in dead material. Xevertheless, there occurs then an 



PATHOGENIC MOULDS. 



671 



active penetration into living tissue — that is, first into the epithelium 
(c, d), but often also into the connective tissue (a, /), and into the 
blood-vessels, and from these portals of invasion there may develop 
metastases in the internal organs. Thus, Zenker has observed hyphge 
and conidia in an abscess of the brain ; and Paltauf has reported a case 
in which a mould-fungus was conveyed from an intestinal ulcer to 
the brain and lung. Schmorl has described thrush-metastases in the 
kidneys. 

Moreover, grow^ths of moulds in the lungs are not always confined to 
dead material or to the cavity of the bronchus, bat it happens, though 
rarely, that they penetrate into the living respiratory parenchyma, form- 
ing small white or yellowish, nodular masses, within which the lung tissue 
is necrotic, while in the neighborhood there is formed an inflammatory 
infiltration. In the injured cornea they may likewise penetrate into the 
tissue and cause necrosis and inflammation. 

Local colonizations of moulds which penetrate into living tissue 
cause a more or less marked irritation of the surrounding tissues, and 
give rise to tissue-degenerations (Fig. 509, c) and inflammation. Such 
changes may be observed in mycosis of the lung, as well as of the intes- 
tine (c, d, f) and ear. \Aniien invading the lungs they form growths of 
hyiDhsB which resemble the granules of actinomycosis, and are surrounded 
by collections of cells. Their action, however, is always limited, and 
they produce no substances which are injurious to the organism as a whole, 
or cause symptoms of poisoning. The frequently reported finding of 
moulds in abscesses of the subcutaneous tissues and internal organs are 
probably to be interpreted as due to the fact, that along with the bac- 
teria causing the suppuration, moulds also get into the tissues, as well 
as into the circulation. A general spreading of mould-fungi does not 
occur in these cases, in that the further development of the same is con- 
fined to the place of the metastasis. 

The form of moulds which are saprophytic, or to a limited extent 
parasitic, in man, belong to the Mucor, Aspergillus, and Eurotium gen- 
era. From the ear various species have been obtained: Aspergillus fumi- 
gatus (Fresen), Aspergillus flavus or flavescens (Brefeld, AYreden), As- 
'pergiUus niger or nigricans (Van Tieghem, Wreden, Wilhelm), Aspergillus 
nidulans (Eidam), Eurotium malignum (Lindt), Mucor corymMfer, and 
Trichothecium roseum ; and, in so far as known, these are the same species 
which occasionally occur in the respiratory tract. 

In the majority of cases it is necessary, in order to determine the 
variety of mould, to make cultures upon suitable nutrient media (decoc- 
tion of bread, bread-agar, potato, gelatin, etc.). On these the conidia 
which are sown grow out into germ-tubes, and form simple or branched, 
unicellular or multicellular threads, on which arise the peculiarly con- 
structed fruit-bearers characteristic of the species, which eventually pro- 
duce conidia. Many also form spores through the copulation of cells of 
the mycelia, especially when the supply of oxygen is lowered (Brefeld, 
Siebenmann). 

In the mucors there appear ^^^^^12! fruit -hearers (Fig. 510, c), which 
according to the species are either single or branched, and on the ends of 
which there are knob-like swellings from which the sporangia (d) — that 
is, spherical vesicles filled with conidia-spores — grow. 

Mucor corymMfer, for example, forms branched fruit-bearers (Fig. 
509, c). The sporangia (d) on the ends possess a smooth membrane and 
enclose at the time of ripening yellowish conidia-spores. 



672 



THE PATHOGENIC MOULDS AND YEASTS. 




Tig. r>l).—Mtir,,r nj-ririnijii ti- m irurcirK-Hti- in iculture upon 
glass-slide) . a, Aei'ial Lypbte ; &, mycelia lying witliin the nutri- 
ent gelatin ; c, branching fruit-bearers ; tU sporangia. X 100. 



The aspergilli form conidia-hearers, wliicli swell out spherically above, 
and then produce numerous sterigmata — that is, cone-like outgrowths, 

radially arranged, thickly 
crowded, and sprouting 
out from the upper half 
of the sphere. From each 
sterigma a cliain of conidia 
is later constricted off (Fig. 
511, «, h). 

The iotanical position of 
the fungus of thrush (aphthae) 
is still unsettled. Form- 
erly it was called Oidium 
albicans, and classed with 
the family Oidium, which 
occurs in different species 
in the form of filmy coat- 
ings upon organic sub- 
stances. \\Tien cultivated 
from conidia it produces 
hyphse which become 
jointed and develop coni- 
dia through a transverse division of the threads, but form no peculiar 
fruit -bearers. 

According to Eees, Grawitz, Rehrer, the thrush-fungus grows by 
budding and by the ijroduction of mycelia and conidia, which in turn 
I)roduce at their ends, by a process of constriction, new conidia, in a 
manner similar to that which takes place in the forms of mycoderina 
belonging to the yeast -fungi. 
Consequently this fungus should 
be designated 2Iycoderma albi- 
cans. Linossier and Eoux are, 
however, of the opinion that the 
thrush-fungus does not belong 
at all to the saccharomycetes, 
and they regard its classification 
at the present time as imiDOSsi- 
ble. Cao, who has investigated 
numerous varieties of oidium, re- 
gards the oidia as a well-defined 
class of fungi standing between 
the blastomycetes and the hy- 
j)homycetes, which they ap- 
proach through their production 
of my celia. 

According to Plant the 
thrush-fungus is identical with a mould, Monilia Candida, which occurs 
frequently in nature. Kehrer suspects that it is one of the higher moulds 
which has become degenerated through parasitism. 

According to ^sevmayer all mrieties of yeasts are resistant to the digestive juices, 
and may pass through the human intestinal tract Avithont being killed. Witliout the 
coincident introduction of some fermentable substance tliey are harmless. They exert 
an influence upon the intestinal canal only when fermentable substances are introduced, 
whereby at the high temperature of the 'body abnormal products of fermentation are 
produced having an irritating action upon the intestinal tract. 




Fig. 511.— Hvphce with conidia-bearersof ^^pergi7?MS 
furnigatus. a. Fruit-head in optical cross-section; h, 
fruit-head seen from above. X 275. 



PATHOGENIC BLASTOMYCETES. 673 

Basse found (1894) great numbers of yeast-cells developing in the diseased areas 
present in a woman, thirty-one years of age, who died from multiple inflammations of 
the bones, skin, lungs, kidneys, and spleen, partl}^ tumor-like and partly abscess-form- 
ing. According to his findings it may be regarded as certain that the yeast was the 
cause of the disease. The yeast could be easily cultivated upon suitable media. Mice 
w^ere particularly susceptible to inoculation, dying in from four to eighty-three days 
after the injection. At death the yeast-cells were found to have markedly increased 
both at the point of inoculation, and also in the internal organs. A proliferation of 
tissue occurred only after a long duration of the infection. 

Buschke found yeasts in multiple ulcers of head and neck, arising from acne-like 
lesions. Gilchrist and Stokes found yeasts in a lupus-like affection of the skin. 

Sanfelice experimented wath yeasts from fruit- juices, and found among these one 
pathogenic for guinea-pigs {Saccharomyces neoformans) and one pathogenic for chickens 
and dogs {Saccharomyces litltogenes). Curtis found, in multiple proliferations of the 
skin resembling myxosarcoma, yeast-cells which were pathogenic for rats, mice, and 
dogs. 

Sanfelice, Corsclli, Frisco, Boncali, Binaghi, Leopold, and others believe that blasto- 
mycetes may be the cause of true tumors, sarcoma and carcinoma ; but true tumors have 
never yet been produced experimentally b,y inoculations of yeast-cells or by injections 
of the same into the blood. Only suppurations and inflammatory tissue-proliferations 
have been produced by such experiments ; and the finding of yeast-like structures in 
true tumors, even if part of these were true yeast-cells, does not permit of the conclu- 
sion that tumors are caused by yeasts (cf. § 122). 

According to investigations by Kocli, Loffler, LicMheim, RiXckel, and Lindt, the 
conidia of Aspergillus fumigatus, A. flacescens, A. nidulans, Eurotium malignuin ; Mu- 
cor rhizopodiformis, 31. corymbifer, M. pusillus, andil/. ramosus, grow at the bodj^ -tempera- 
ture, and, when introduced into the blood-current of animals, grow into the tissues and 
form hyphse, although there is no new formation of conidia, and consequently no pro- 
gressive infection of the animal extending bej'ond the area within which the spores 
have been introduced. Conidia of Mucor rliizopodiformis and M. corymbifer grow, 
when introduced into the blood-stream of rabbits, chiefly in the kidnej^s and the lym- 
phatic apparatus of the intestines, where they cause a haemorrhagic inflammation. 
According to Cao, there are different species of oi'dia which, when injected into 
rabbits, cause inflammations, abscesses, or proliferations of granulation tissue; and 
many produce also a toxic action upon the organism. 

Aspergillus mycoses of the respiratory tract are not rare in animals, espe- 
cially in birds, and the proliferating mj^celia cause tissue-necrosis and inflammation. 
According to CJiantemesse, Aspergillus f umigatus causes in pigeons diseased conditions 
of the mouth, lungs, liver, and kidney, that of the first two organs resembling diph- 
theria, that of the latter tw^o closely resembling tuberculosis. It may, therefore, be 
designated pseudotuberculosis aspergillina. According to Potaiti the infection may be 
transmitted to man and give rise to ulcerative diseases of the lung. 

Eurotium and Aspergillus, according to Siebenmanii, are two different families, 
having, however, a close resemblance to each other, in that the mycelia and conidia are 
similarly formed. The essential differences between the two lie in the fact that Euro- 
tium forms perithecia in the form of shining, light-yellow or sulphur-yellow, translu- 
cent bodies the size of a grain of sand, delicate and easily crushed ; while the true 
Aspergillus forms hard, woody sclerotia usually embedded in a thick, white matted 
mass of mycelia. The development of these takes place in two periods. The second 
part of the development occurs only when the sclerotium finds a lodgment upon a 
moist substratum. 

Aspergillus flavus of Brefeld {Eurotium Asperillus flavus of de Bary) forms golden 
yellow, green, and brow^n growths; round, yellow, olive-green, or brown fruit-heads; 
round, rarely oval, sulphur-yellow to brown conidia with minute warts on the surface; 
diameter 5-7 fj,. Aspergillus fumigatus of Fresen {Aspergillus nigrescens of Bobin) forms 
green, bluish, or gray growths; the fruit-heads are long, in shape resembling an in- 
verted cone; conidia, round, rarely oval, smooth, mostly clear and colorless; diameter 
2.5-3 Aspergillus niger of Tan Tieghem {Eurotium Aspergillus niger of de Ba/ry) forms 
dark chocolate-brown growths; conidia are round, brownish-black, or grayish-brown 
when ripe; surface smooth or warty ; diameter 3.6-5//. 

Aspergillus can develop upon the injured cornea and give rise to purulent inflam- 
mation. Leber {Graefe's Arch., xxv.) cultivated it upon the cornea and in the anterior 
chamber of the eye of the rabbit. Finallj^ Aspergillus also appears in the pelves of 
the kidneys. Babes (Biol. Gentralbl., ii.) found the conidia and hyphae of a mould in 
ulcers of the skin which were covered by scabs, and gave to it the name of OMium sub- 
tile cutis. 

35 



674 



THE PATHOGENIC MOULDS AND YEASTS. 



Literature. 

{Pathogenic Blastomycetes. ) 

Acevoli: Blastomiceti nei neoplasmi. Cbl. f. Bakt., xx., 1896 
Binaghi: Blastouiyceten in Epitiieliomen. Zeitsclir. f. Hyg., xxiii., 1896. 
Buschke: Die Hefenmykosen. Samml. klin. Vortr., No. 218, Leipzig, 1898 (Lit.). 
Busse: Die Hefen als Krankheitserreger, Berlin, 1897 (Lit.); Pathogene Helen. 

Ergebn. d. allg. Path., v., Wiesbaden, 1900 (Lit.). 
Corselli u. Frisco: Pathogene Blastomyceten. Cbl. f. Bakt., xviii., 1895. 
Curtis: Sacchavomycose humaine. Ann. de I'lnst. Pasteur, 1896. 
Evans: Blastomycosis of Skin from Accidental Inoculation. Jour, of Amer. Med. 

Assn., 1903. 

Foulerton: Pathogenic Action of Blastomycetes. Jour, of Path., vi., 1899. 
Frothing-liam : Tumor-like Lesion in the Lung of a Horse Caused by a Blastomyces 

(Torula). Jour, of Med. Res., 1902. 
Gilchrist and Stokes: Pseudolupus Caused by a Blastomyces. Jour, of Exp. Med., 

iii., 1898. 

Gilkinet: Sort des levures dans I'organisme. Arch, denied, exp., ix., 1897. 
Hyde: Blastomj^cetic Dermatitis. Jour, of Amer. Med. Assn., 1902. 
Leopold: Aetiologie d. Care. u. pathog. Blastomyceten. Arch. f. Gyn., 61 Bd., 1900. 
Maffucci u. Sirleo: Blastomyceten als Infectionserreger. Zeitsclir. f. Hyg., xxvii., 
1898. 

Neumayer: Wirk. versch. Hefearten auf d. tliier. u. menschl. Organisnius. Arch. f. 
Hyg., xii., 1892. 

Nichols: The Relation of Blastomycetes to Cancer. Jour, of Med. Rea. 1902. 
Ormsby and Miller : Sytemic Blastomj^cosis. Jour. Cut. Dis., March, 1903. 
Rabinowitsch : Pathogene Hefearten. Zeitschr. f. Hyg., xxi., 1895. 
Ricketts: Oidiomycosis (Blastomycosis) of the Skin and its Funsri. Jour, of Med. 
Res., 1901. 

Roncali: Blastomyceten in Saikomen. Cbl. f. Bakt., xviii., 1895. 

Sanfelice: Pathogene Wirkung d. Blastomyceten. Cbl. f. Bakt.. xvii. and xviii.; 

Zeitschr. f. Hyg., xxi., xxii., 1896; xxvi., 1897; xxix., 1898. 
Weis: Four Pathogenic Torulae (Blastomycetes). Jour, of Med. Res., 1902. 
Wlaeff: Role des blastomycetes dans I'organisme. Soc. Anat., Paris, 1900. 

{The "Moulds and the Mould- Mycoses.) 

Baumg-arten : Die patliogeneu Hyphomyceten. Deut. Medicinal-Zeitung, 1884; Lehr- 

buch der path. Mykologie, 1889 ; Jahresbericht. 
Bezold: Ueber Otomykosis. Zur Aetiologie der Infectionskrankheiten, Miinchen, 1881, 
Block: Ueber Pilzbildung im tliierischen Gewebe. Inaug. -Diss. , Stettin, 1871. 
Boyce: Remarks upon a Case of Aspergillus Pneumonomvcosis. Jour, of Path., i., 

1892. 

Chantemesse : Pseudotuberkulose, auf Pilzwucherungen beruhend. Cbl. f. allg. 
Path., i., 1870. 

Cohnheim: Zwei Falle v. Mykose der Lungen. Virch. Arch., 38 Bd., 1865. 
Dubreuilh: Les moisissures parasitaires de I'liomme. Arch, de med. exp., iii., 1891 
(Lit.). 

Dusch u. Pagenstecher : Eiu Fall von Pneumonomykosis. Yirch. Arch., 11 Bd., 
1857. 

Friedreich: Pneumonomykosis aspergillina. Virch. Arch., 10 Bd., 1856. 
Flirbringer: Lungenmykose beim Menschen. Virch. Arch., 66 Bd., 1876. 
Grawitz; Schimnielvegetation im thier. Organismus. Virch. Arch., 81 Bd., 1880. 
Hiickel: Mucor corymbifer (im auss. Ohr). Beitr, v. Ziegler, i., Jena, 1885. 
Kitt: Mykose d. Luftwege d. Tauben. Deut. Zeitschr. f. Thiermed., vii., 1882. 
Kotliar;"^ Contrib. a I'et. de la pseudotuberculose aspergillaire. Ann. de I'lnst. Pas- 
teur, viii., 1894. 

Leber: Grafe's Arch,, xxv. ; Die Entstehung der Entziindung, Leipzig, 1891. 

Lichtheim: Pathogene Mucorineen. Zeitschr. f. klin. Med., vii., 1883. 

Lindt: Neuer pathogener Schimmelpilz aus d. Gehorgang. Arch. f. exp. Path., 

xxiv., 1889; Ueb. einige pathogene Schimmelpilze. Arch. f. exp. Path., xxi., 

1886; xxv., 1889. 
liOffler: Mittheil. a. d. K. Gesundheitsamte, Berlin, 1881. 



FAVUS. 



675 



Obici: Pathogene Eigeusch. d. Aspergillus fumigatiis. Beitr. v. Ziegler, xxiii., 1898 
(Lit.). 

Oppe: Scbimmelmykose d. liarten Hirniiaut. Cbl. f. allg. Path., 1897. 

Pearson: Pneumonomycosis due to the Aspergillus Fumigatus. Proc. of the Path. 

Soc. of Philadelphia, 1900. 
Perroncito: Mycose aspergillaire. Arch. ital. de biol., vii., 1886. 
Podack: Aspergillusmykoseu im Respirationsapparat. Virch. Arch., 139 Bd., 1895 

(Lit.). 

Potain: Un cas de tuberculose aspergillaire. L'UDiou med., 1891. 

Pusch: Fadenpilze bei Thierkrankheiten. Ergebn. d. allg. Path., iv., 1899. 

Renon: Rech. clin. et exp. sur la pseudotuberculose aspergillaire, Paris, 1893; ^tnde 

sur I'aspergillose chez les animaux et chez rhomme, Paris, 1897 (Lit.). 
Ribbert: Der Untergang pathogener Schimmelpilze im Korper, Bonn, 1887; Ueber 

wiederhoite Infection mit pathogenen Schimmelpilzen. Deut. med. Woch. , 1888. 
Roeckl: Ueber Pneumonomykosen. Deut. Zeitschr. f. Thiermed., x., 1884. 
Rothwell: Experimental Aspergillus. Jour, of Path., vii., 1900. 
Saxer : Pneumonomykosis aspergillina, Jena, 1900. 

Sclienck: Subcutaneous Abscess Caused by a Fungus. J. Hopkins Hosp. Bull., 1898. 

Schmorl: Ein Fall von Soormetastase in der Niere. Cbl. f. Bakt., vii., 1890. 

Schiitz: Das Eindringen von Pilzsporen in d. Athmungswege u. die dad. bedingten 
Erkrankungen d. Lune, Pilz d. Hlihngrindes. Mittheil. a. d. K. Ges.-Amte, Ber- 
lin, 1884. 

Siebenmann : Die Fadenpilze Aspergillus flavus, niger u. fumigatus, Eurotium re- 
pens, u. Aspergillus glaucus, Wiesbaden, 1883; Die Schimmelmykosen d. Ohres, 
Wiesbaden, 1889. 

Soltmann: Soor. Eulenburg's Realencyklop., xxii., 1899. 

Virchow: Beitr. z. Lehre v. d. pflanzliclien Parasiten. Virch. Arch., 9 Bd. , 1856. 
Zenker : Hirnabscess. Jahresber. d. Ges. f . Natur- u. Heilk. in Dresden, 1861-62. 
Zlirn: Die Schmarotzer in u. auf dem Korper unserer Haussaugethiere, ii., Weimar, 
1887. 

(Thrush.) 

Bohn: Soor. Gerhardt's Handb. d. Kinderkrankh. . iv. 

Cao: Oidien u. Oidiomykose. Zeitschr. f. Hyg., 34 Bd., 1900 (Lit.) 

Fischer u. Brebeck; Zur Morph. u. Syst. d. Kahmpilze. Monilia Candida u. d. 

Soorerreger, Jena, 1894. 
Grawitz: Parasit des Soors. Virch. Arch., 103 Bd., 1886. 
Heller: Zur Lehre v. Soor. Deut. Arch. f. klin. Med., 55 Bd., 1895. 
Kehrer: Der Soorpilz, Heidelberg, 1883. 

Linossier et Roux: Champignon du muguet. Arch, de med. exp., 1890. 

Plant: Syst. Stellung d. Soorpilzes, Leipzig, 1885; Neue Unters. z. syst. Stellung d. 

Soorpilzes, Leipzig, 1887. 
Rees: Soorpilz. Sitzungsber. d. Phys.-med. Soc. zu Erlangen, 1877, 1878. 
Sclimidt, M. B. : Die Localisation d. Soorpilzes in den Luftwegen u. sein Eindringen 

in das Bindegewebe der Oesophagusschleimhaut. Beit. v. Zeigler, iii., 1890. 
Steiner: Zur Pathogenese d. Soorpilzes. Cbl. f. Bakt., xxi,, 1897. 
Teissier: Champignon du muguet. Arch, de med. exp., ix.,., 1897. 

§ 179. Thread=fungi are to be regarded as the exciting cause of 
disease in certain affections of the skin, as favus, herpes tonsurans, 
pityriasis versicolor, erythrasma. In all of these diseases the ejpithellal 
parts of the skin contain colonies of hyphse and conidia, and there re- 
mains no doubt that their presence causes in part tissue-degenerations, 
and in part proliferations and inflammations. 

The fungus of favus (Fig. 507) is usually called Achorion Schonleinii 
(discovered by Schonlein in 1839). 

Favus (tinea favosa, scald-head) affects particularly the hairy portions 
of the head, more rarely other regions, as, for example, the substance of 
the nails. It is characterized by the formation of di&cs (favus scutula), 
varying in size from that of a lentil to that of a five-cent piece, of a sul- 
phur-yellow color, and indented or pierced by a hair. In an abortive 
course it may merely form scales similar to those of herpes. 



676 



THE PATHOGENIC MOULDS AND YEASTS. 



According to Kaposi, the faviis scutulum originates as a small, punc- 
tiform, yellow focus lying under the epidermis and penetrated by a hair. 
This grows in a few weeks to the size of a lentil and then forms a sul- 
phur-yellow, indented disc showing through the upper layers of the 
skin. The scutulum consists of hyphse and conidia spores, and lies in a 
cup -shaped depression of the skin, beneath the horny layer which is 
drawn away above it. If the mass be removed during life, the cavity 
shows a red moist surface. The favus itself forms a white, crumbling 
mass which is easily disintegrated in water. 

If the scutula are not remo^ ed, they join together to form larger 
masses. When the ei)idermis is desquamated the favus-mass becomes 
exposed and dries up into a yellowish-white, mortar-like material. The 
hairs appear lustreless, as if covered with dust, and are easily pulled 
out, since the mycelia and conidia of the fungus penetrate into the hair- 
shaft and hair-bulb, as well as into the sheath of the hair-root. 

Through the growth of the fungus-masses the hairs may not only be 
shed, but the papillae may become atrophic. At the same time there is 
produced in the neighborhood of the hair-follicle a more or less intense 
inflammation which may take on an eczematous character. 

The development of achorion in the nails (onychomycosis favosa) gives 
rise to sulphur-yellow deposits or uniform thickenings of the parenchyma 
of the nails with simultaneous loosening and cheesy disintegration of the 
same. 

Trichophyton tonsurans, the fungus of herpes tonsurans barber'' s 
itch/^ ringworm ^^), consists of long narrow threads, branching but little, 
and with few conidia. It forms no scutulous masses, but penetrates easily 
into the hair-shaft, and makes the hairs brittle. It shows certain differ- 
ences of growth, according to whether the herpes develops upon hairy 
surfaces or upon areas devoid of hairs. 

Herpes tonsurans cajnUitii forms bare discs varying in size from that of 
a five-cent piece to that of a dollar. These spots in which the hairs are 
broken off short look like places in which the hair has been badly shaven. 
The surface is smooth or covered with scales, and somewhat reddened at 
the border of the disc. If the fungus-threads penetrate into the hair- 
follicles, pustules and scabs are formed. Such discs may appear in many 
places, and may constantly increase in size until healing finally takes 
place. 

On places devoid of hairs the herpes forms vesicles (Hopes tonsurans 
vesiculosus) , and red scaly spots, discs, and circles (Herpes tonsurans squa- 
mosus). At times red spots appear in numerous places; these quickly 
spread, and as rapidly heal. The fungus is found between the upper- 
most laj^ers of the epidermis, just beneath the stratum corneum (Kaposi). 

If trichophyton develops in the nail, the nail becomes cloudy, scales 
off, and is easily broken — a condition designated as onychomycosis tricho- 
phytina. 

Sycosis parasitaria arises through the fact that the development of the 
fungus is accompanied by a severe inflammation of the hairy parts of 
the skin, leading to infiltration and suppuration — that is, to the forma- 
tion of pustules, abscesses, and papillary proliferations. According to 
Kaposi and others eczema marginatum is also caused by the trichophy- 
ton tonsurans. The condition occurs in those regions where two surfaces 
of skin come into contact with each other and are macerated by sweat ; 
and is characterized by the formation of vesicles, pustules, and scabs, 
which are situated in the periphery of a pigmented surface. 



PITYRIASIS VERSICOLOR. ERYTHRASMA. 



677 



Microsporon furfur, the fungus of pityriasis or mycosis versicolor 
or dermatomycosis furfuracea, occurs likewise in the form of hyphi© 
and couidia, which are somewhat smaller than those of other skin-fungi. 
The pathological changes produced by this fungus are characterized by 
the formation of pale yellow or yellowish-brown to dark- brown and 
brownish-red spots, varying in size from that of a lentil to that of the 
hand, sometimes smooth and shining, at other times dull and exfoliating, 
and of irregular shape. They inay be spread uniformly over large areas 
of skin ; and are found chiefly upon the trunk, neck, and flexor surfaces 
of the extremities, but never upon the hands, feet, or face. 

Microsporon minutissium is the name given to a thread-fungus, 
which is found in the skin affection known as erythrasma (von Baren- 
sprung). The disease is charac- 
terized by the formation, on the 
inner side of the thigh, of brown 
or reddish-brown patches, which 
are only slightly scaly, and may 
be as large as the palm of the 
hand. The fungus is found in 
the epidermis, and is smaller than 
that of pityriasis. 

The thread-fungi occurring in 
the diseased areas of the skin 
may be culti\ ated upon proper 
media (agar-agar, agar-giycerin, 
gelatin, potatoes, blood-serum, 
etc.), and on such the conidia de- 
velop into single and branching 
threads, which become jointed 
(Fig. 512, «), and form chains of 
short cell (b). Club-like forma- 
tions which frequently appear 
upon the ends of the threads in 
cultures, are regarded by Quincke 
and Elsenberg as imperfect spo- 
rangia. The botanical i^osition of 
these fungi is not yet determined ; and nothing is known with certaintj' 
concerning their distribution outside of the human and animal body. 

According to Quincke, three forms of fungi occur in favus-niasses, 
two of these being \'arieties of one species of fungus. Elsenberg found 
only two, which he regards as being varieties of the same si^ecies. Pick, 
Plant, and Biro believe firmly in the etiological unity of favus. 

Sabouraud advances the view that the fungi causing trichophytosis 
represent very different species, all of which belong to the genus Botry- 
tis. Krosing distinguishes three groups of trichophyton-fnngi according 
to the different appearances of the cultures on jDotato, and emphasizes, 
moreover, the differences in their organs of generation and fructification. 
Rosenbach, who has studied the moulds occurring in deep suppurating 
inflammations of the skin, differentiates several trichophyton-fungi as 
the cause of the^se affections. 

According to Spietschka the Microsporon furfur may be cultivated 
from the scales of the skin, and in cultures can be very well differentiated 
from the other pathogenic thread-fungi. Through the inoculation of the 
fungus a typical mycosis may be produced in man. 




Fi(.. Culture of Trichniilnjtnn tonsurans, a. 
Branching threads with Inner joints which have deU- 
cate walls ; h, threads with thi<-k-walled, short seg- 
ments, some of them being spherical. X ^0. 



6Y8 



THE PATHOGEXIC MOULDS AND YEASTS. 



From the great iiiiinber uf recent investigations by various writers it 
is impossible to deduce anything definite concerning the number of kinds 
of favus- and trichophyton-fungi. It is, however, evident from these 
investigations that the natui e of the nutrient medium is of great influence 
on the character of the growth i Sabouraud, ^Vaelsch), and the difference 
in findings is to be referi-ed in a great measure to differences in the nu- 
trient media on whicli the moulds wei-e grown. 

Inocuhitions with fungi grown in cultures, into the skin of human 
beings, rabbits, mice, etc., which weie made by Grawitz, Boer, Miinnich, 
and others, gave partly negative, partly positive results. According to 
Plant the inoculations uexer give positive results when spore-formation 
has already taken place in the cultures. 

^'o// Hehra has described [^^yielitr mtd. Blotter. 1881: "Die Krankh. Verand. d. 
Haut," Braunschweig, 1881) as dtniiatoniijensis dirf'ai^'i jieToraiu a peculiar itching der- 
matosis, which occurs on the elbow and bend of the knee, and is thought to be caused 
by fungi, which are like those oi pityrli !.■<(.•< rt i-:<ic':'hyr. 

Favus and Tierpes t<i/i.^'iraiis occur als{.) in domestic animals, as well as in mit-e and 
rats (cf. Friedehrrfu r and Frdluier. " Lelii'. d. spec. Pathologic der Hausthiere "). 
^yaeUd^ inoculated human individuals with t'avus-fimgi. which he had cultivated from 
mice affected with favus, and obtained typical favus scutulari^. 

Intravenous injections of favus-fnugi into ral)bits iBukovsky) produced in the 
lungs of these animals a form of pseudotuberculosis: and celhdar nodules are found in 
which fungus threads have developed in a manner suggesting the lesions of actinomy- 
cosis. After a time the fungi die. 

In invertebrate animals there not infrequently occur diseases produced hj my- 
celium-fungi. Tlius B'Arytis Bassimu causes the so-called mv scar dine in silkw^orms: 
Cardyceps nuUtaris destroys the injurious pine-spider Ga^ti-opachia piui: Tarichium 
inegasperinuiit. a black-colored fungus, kills the destructive <^arth-caterpillar Agrotis 
segetum. Fungi belon-iing to the family Fmp'is.i attack especially the caterpillars of 
the cabbage-butterfly \Einjaisa radf''" /i.^). and the house-fly {Emp"sa mnsc<]E). their 
mycelia growing all through the caterpillar and Anally killing it. Arfiyla prolifera, 
ac-c-ording to (r/^/A/v s^/( r. d. Muncltritr ThierarzimschuU. 188'2-83). grows througk 

the musculature of crayfish, and is the cause of the craytish-pest. 



Literature. 

{JFlip Fungi of the Dermatonii/coses.) 

Ad.am.son: Parasites of Ringworm.. Jour, of Dermatol., vii.. 1895. 

Biro: I'nters. liber d. Favuspilz. Arch. f. Derm., 1893. 

Boer: Biologic des Favus. Yierteljahrsschr. f. Derm. u. Syph.. xiv., 1887. 

Bonome: Tricofltiasi dermica a forma pemfigoide et polineurite tricofitica in individuo 

affetto da tabe dorsale. Arch, per le Sc. Med., xvi.. 189'2. 
Bukowsky; Eigenschaften d. Achorion Schonleinii. Arch. f. Derm.. 51 Bd., 1900. 
Campana: Tricliopliytiasis dermica. Arch. f. Derm. u. Syph.. 1889. 
V. Diiring': Dermatoiiiykosen. Eulenburg"s Jahr. , 1896 (Lit.). 

Elsenberg-: Leber den Favuspilz bei Favus herpeticus. Arch. f. Derm.. 1889, 1890. 
Fabry: Leber Favus. Arch. f. Derm.. 1890 : Onvchomvkosis favosa. Arch. f. Derm., 
1890. 

Fox and Blaxall: Pluralitvof Rino:worm Fungi. Trans, of the Path. Soc. of London, 
xlviii.. 1897. 

Grawitz: Soor. Favus u. Herpes tonsurans. Yirch. Arch.. 108 Bd.. 1886. 

Krai: Polymorphismus pathogener Hyphomyceten. Arch. f. Derm., xxvii., 1894. 

Krdsing: 'Trichophytonpilze. Arch, f. Derm.. 35 Bd.. 1896. 

Mazza: Trichophytonkultiu-en. Arch. f. Derm., xxiii., 1891. 

Mliller: Favus u. 'Herpes tons. Correspbl. f. Schweizer Aerzte. 1897. 

Neebe u. Unna: Die bisher bekannten neuen Favusarten. Cbl. f. Bakt.. xiii., 1893. 

Pick: Favus. Zeitschr. f. Heilk., xii., 1891: Stand d. Dermatomykosenlehre. Arch. 

f. Derm., xxix. Cbl. f. Bakt.. xvii.. 1895; Favusfrage. Arch. i. Derm., xxxi., 

1896. 

Pick u. Krai: Lnters. liber den Favus. Arch. f. Derm., 1891. Erganzungsheft. 
Plo-ut: Beitrag zur Favusfrage. Cbl. f. Bakt., xi., 1892. 



THE DERMATOMYCOSES. 



679 



duincke: Ueber Favuspilze. Aicli. f. exper. Path., xxii., 1886; Monatsh. f. prakt. 

Derm., vi., 1887, viii., 1889; Arch. f. Derm., 31 Bd.. 1895. 
Roberts: The Physiology of the Trichophyton. Jonr. of Path., iii., 1895. 
Rosenbach.: Ueber die tieferen eiternden Schimmelerkrankungen d. Haut, Wiesbaden, 

1894. 

Sabouraud: Trichophj^tie. Ann. deDerm., 1892; Trichophyties a dermite profonde. 
Ann. de I'Inst. Pasteur, vii., 1893; Mvcose innominee de I'homme. lb., viii., 
1894. 

Spiegler: Ekzeraa marginatum. Arch. f. Derm.. 38 Bd.. 1897. 
Spietschka: Microsporon furfur. Arch. f. Derm., 37 Bd., 1896. 
Unna: Drei Favusarten. Fortschr. d. Med., x., 1892. 

Waelsch.: Anatomic des Favus. Arch. f. Derm., 31 Bd., 1895; Anatoraie d. Tricho- 
phytosis, lb., 35 Bd., 1896; Mannigfaltigkeit d. Wachsthums d. pathog. Schim- 
melpilze. lb., 37 Bd., 1896; Anatomic d."^ Pityriasis versicolor. lb., 38 Bd., 1897; 
Favus bei Thieren u. dessen Bezieli. z. Favus d. Menschen. Prag. med. Woch., 
1898. 



CHAPTER XII. 



The Animal Parasites and the Diseases Produced by 

Them. 

I. Protozoa. 

§ 180. Of the Protozoa occurring as parasites in man, only a small 
nimiber was known up to a few years ago ; and even the known forms 
possessed but slight significance, since there could be ascribed to them 

no marked influence upon the tissues. 
Through the investigations of the last few 
years, however, different forms have been 
recognized as the cause of morbid proc- 
esses; and it is quite possible that there 
are still other protozoa capable of exciting 
pathological changes in the human body. 
The forms already recognized are repre- 
sentatives of all four classes of protozoa. 

Of the Rhizopoda there occur in the in- 
testine three amoebcT, known as the Amceha 
coli vulgaris, the Amoeha coJi niifis (Eoos, Quincke), and the Amorha dys- 
euterice (Kartulis, Osier, Councilman, Lafleur, Kruse, Pasquale). The 
Amoeba dysenterise is certainly distinguishable from the other two, 
while the Amoeba coli vulgaris and the Amoeba coli mitis resemble each 
other very closely, and may possibly be identical. 

The Amoeba coli vulgaris is a harmless intestinal parasite which is 
not infrequently resent in the intestine (Eoos, Kruse, Pasquale). The 
Amoeba coli mitis was observed by Eoos and Quincke in cases of chronic 
enteritis in patients who had always lived in Xorth Germany. 

The Amoeba coli mitis consists, according to Eoos, of a protoplasmic 
cell-bodj% from 25-35 /a in diameter (in the spherical condition). It ex- 
hibits slow movements, and very frequently encloses foreign bodies, for 
example, bacteria and food-remains (Fig. 513, a). Besides the motile 
form, there occur, according to Eoos, also encysted, spherical forms 
which are surrounded by a double -contoured membrane, and enclose 
clear, round vesicles in their interior (Fig. 512, b). VThen fed to ani- 
mals (cats) no pathogenic properties are disclosed. 

The Amoeba dysenteriae (identical with the Amoeba coli described by 
Loesch) has a diameter, according to Eoos, of from 15-25 a, but accord- 
ing to Kruse and Pasquale, from 10-50 a. In the cell -body there may 
be recognized a homogeneous ectoplasm and a variable granular ento- 
plasm, the arrangement of which varies according to the form of the 
animal (Fig. 514, a). By staining, a nucleus may be made visible within 
the cell. The cells are capable of active movement, and assume thereby 
the most varied shapes (d). They very often contain foreign bodies, 
particularly red blood-cells or remains of such (&), or are studded with 

680 




AMCEBA. INFUSORIA. 



681 






Fig. 514:.— Amceba dijsenteriw sive Amceba eoU felis. 
(After Roos.) a, Amoebse without inclusions; h, amoebse 
containing blood ; c, amoeba? witb large vacuoles in their 
protoplasm ; d, young forms ; e, encysted forms. X 6(d5. 



clear vacuoles (c). According to Eoos, tliej^ may also become en- 
cysted (e). 

According to investigations by Koch, Kartulis, Kruse, and Pasquale, 
they are invariably present in the dysentery prevailing in Egypt, and 
are usually also demonstrable 
in the dejecta. They have 
also been observed in cases of 
dysentery in Eussia (Loesch, 
Massiutin), in America (Os- 
ier, Councilman, Lafleur, Lutz, 
Dock), in Germany (Roos), 
and in Austria (Kovacs) . Ac- 
coiding to investigations by 
Kartulis, Councilman, La- 
fleur, Kovacs, Roos, Kruse, 
Pasquale, and others, it can- 
not be doubted that they are 
of some significance in the 

origin of certain forms of dysentery. It is only questionable whether 
they alone, or only with the aid of changes produced by bacteria, are 
able to bring about pathological changes. In support of the latter 
theory is the fact that, when present in the tissues, they are always ac- 
companied by bacteria. 

Amoebic dysentery is characterized by the occurrence of a hsemor- 
rhagic catarrh, and by the formation of circumscribed ulcers with under- 
mined edges. The amoebie (Councilman, Lafleur, Roos, Kruse, Pas- 
quale) increase not only in the intestinal mucosa, but also penetrate into 
the mucosa and submucosa, and there form large colonies, in the region 
of which the tissue undergoes necrosis without the formation of any large 
amount of exudate. By the rupture of the submucosal foci through the 
mucosa there are formed ulcers with undermined 
edges, which, gradually increasing in size, may attain 
large dimensions. 

If abscesses of the liver arise during the course of an 
amoebic dysentery, these may also contain the amoebie 
in addition to bacteria ; and it may be assumed that 
the former also take part in the destruction of the 
liver tissue. 

The amoebce of dysentery are pathogenic for cats, and, 
when fed to them or when introduced into the rectum 
of the animal, cause a rapidly progressive, often fatal 
dysentery, which is similar in all respects to amoebic 
dysentery in man. The amoebse also penetrate into 
the mucosa and submucosa of these animals. 

Of the Infusoria, hoth flagellated and ciliated forms 
occur in man. Of the latter form the best known is 
the Paramaecium or Balantidium coli (Fig. 515). 
This is a large infusorium thickly set with cilise, 
which has been demonstrated many times in the large 
intestine and in the dejecta in cases of diarrhoea, and 
may stand in a causal relation to the intestinal catarrh. Of the flagel- 
late infusoria, there may be mentioned first the Cercomonas intesti= 
nalis (Fig. 516), a pear-shaped form having a spinous process at its 
pointed end, and a flagellum at its blunt end. It has also been found 




Fig. 516.— Balantid- 
ium {paramcecium) 
coli, with two contrac- 
tile vacuoles. (After 
Claus.) a. Mouth; b, 
nucleus ; c, included 
starch grains ; cl, for- 
eign body in the act of 
being extruded. High 
magnification. 



6S2 



THE ANIMAL PARASITES. 



in the intestine in catarrhal conditions, and in cholera and typhoid 
eases. According to Biitschli and Perroncito it is identical with nega= 
stoma entericum of Grassi and Megastoma Intestinale of Blanchard, and 
is in j)art passed off in the foeces in an encysted form (Perroncito), 




Fig. bys.—Cercoinonas i)ite,^ti- Fig. ol~ .—Trichi imoua,s vauin- Fig. 'A^.~Trich<>)no)ias intes- 
nalis. (After Davaine.) afis. (After Kolliker.) tinaUi<. (After Zenker.) 



particularly when no diarrhoea is present. It occurs also in mice, rats, 
cats, dogs, sheep, and rabbits (Grassi), and attaches itself firmly to the 
surface of the intestinal epithelium. 

Kannenberg found a cercomonas in the sputum in a case of lung-gan- 
grene. In association with it there was also found Monas lens, a spherical 
infusorium with a flagellum. Strong reports a similar finding. 

Of the genus Trichomonas an oval infusorium furnished with many 
flagella and a comb-like undulating fringe along its entire length, one spe- 
cies, Trichomonas vaginalis, occurs in the vagina (Fig. 517), and an- 
other. Trichomonas intestinalis, in the intestine (Fig. 518). 

Marchand found trichomonads with four thread-shaped flagella and 
an undulating membrane in the urine of a man. These were probably 
identical with Trichomonas vaginalis, which also possesses four flagella. 
Miura reports a similar observation. Grimm saw flagellated infusoria 
in abscesses of the liver and lung. Lindner found ciliated infusoria in 
the crusts of an itching eczema of the scalp. 

Lowit, on the ground of a thorough investigation, is of the opinion that leukaemia 
is an infectious disease caused by protozoa ; and describes as the cause of the same, two 
parasites, a haemamoeba leuksemise magna and a haemamoeba leukasmise parva (or 

vorax), the first of which occurs in myelogenous leukaemia, the latter in the lymphog- 
enous variety. His opinion is supported by the histological examination of the leu- 
kfemic blood and of the organs changed by the disease, and he succeeded through the 
aid of special staining methods in demonstrating the presence in and upon the white 
blood-corpuscles of small granule-like and large amaba-like bodies, as well as sickle-, 
spindle-, and crescent-shaped structures, and segmented bodies in the morula stage, 
Flagella were also observed. Lowit studied these appearances most thoroughly in a 
case of mj^eliemia; and was able through injections of blood or of pulp made from por- 
tions of organs, into the jugular vein of the rabbits (the injections being directed toward 
the brain), to produce a diseased condition, and to find in the blood of the inoculated 
animal the structures in question, also flagellated forms. Filrst has explained the ap- 
pearances described by Lowit as being nothing more than artefacts, and regards them as 
distorted, swollen, washed-out, and macerated mast-cell granules. Lowit holds to his 
view in spite of this attack, and supports himself chiefly by the fact that his hjBmamoebye 
show a specific staining reaction with watery thionin and iodine, which the mast-cell 
granulations and similar elements do not possess ; and f ui'ther, that the hoemamoebce are 
found in cells without granulation as M^ell as those with granulation, that they sho^w 
characteristic sickle-, whip-, and flagellate-forms, and form bodies even as large as 10 fi 
in diameter, and tinall}- , that they do not occur in normal blood. 

Recently Lowit has reported observations on the spore-like resisting forms of hae- 
mamoeba leukaemiaB magna, which he had seen in the blood-forming organs of a case of 
myelaemia. The earlier described flagellate-forms of the parasite seen in infected rab- 
bits he interprets as forms standing in relation to the sexual reproduction of the hsema- 
moebae, since the amoebae and flagellated forms unite with each other. In man the para- 
site is said to reproduce chiefly by schizogony, in rabbits by sporogonj^ (cf. reproduc- 
tion of coccidia and malarial plasmodia, §| 181, 182). To the parasites of lymphaemia, 



FLAGELLATES. 



TRYPANOSOMA. 



683 



which, according to his latest publication, he tinds in the nuclei of the white blood- 
cells, he gives the name Hmnamceba leukcemia parm intranuclearis. He finds these nu- 
cleoloid bodies also in pseudoleuksemia, most abundantly in the spleen, to a less extent 
in the lymph-glands. 

Henseii found infusoria with one to three flagella in the stomach-contents of a case 
of gastric cancer. Jacohy and Schaudinn describe two ciliated infusoria obtained from 
the intestinal contents of a man suif ering with diarrhoea ; to these Schaudinn gave the 
names Balantidium monatum and J^yctotherus faba. 

Von Leyden Schaudinn (" Leydenia gemmipara, " Sitzber. d. K. Akad. d. Wiss., 
Berlin, 1896) found, in the fluid of two cases of ascites occurring in malignant disease of 
the abdomen, an amoeba, which consisted of colorless gelatinous cells, which put out 
pseudopodia, and showed a hyaline entoplasm and a granular ectoplasm. They were 
found chiefly lying together in groups. 

Protozoa belonging to the flagellates have been many times observed in the blood 
of animals. In 1875 Bdttig reported observations of the flagellates occurring in the 
blood of frogs. In 1877 Leu'is described a flagellate found in the blood of an Indian 
rat. Kent named this Herpetomonas Leicisii. Evans, in 1880, found similar forms in 
horses, mules, dogs, camels, and cattle suffering from surra, a disease which is common 
among these animals in India, and runs a course resembling that of a pernicious anaemia. 
Koch and Wittich described such forms in marmots, Danileiosky (1885) in birds, fishes, 
and frogs. In 1894 Bruce discovered that the tsetse disease {fly disease, nagana) which 
occurs in Zululand and affects the cattle, horses, asses, and dogs of South Africa, is due 
to flagellates transmitted through the sting of the tsetse-fly. 

All the forms of flagellates observed in the blood of different animals are generally 
designated as Trypanosoma sanguinis ) and different species or varieties of the 

same are distinguished. Von Wasielewski classes with. the trypanosoma of Oruby only 
the blood -parasites of frogs and fishes, and would retain for the trypanosoma of mam- 
mals the name Herpetomonas given by Kent. The form known as Trypanosoma san- 
guinis is widely distributed among the wild rats (brown rats and gray rats), the infected 
rats showing no recognizable symptoms. According to von Wasielewski the parasite is 
8-30 long, 2-3// broad, possesses at its posterior end a beak-like process (Fig. 519, A), 
on the anterior a flagellum (d), and on its side an undulating membrane (c). By proper 
staining (Romanowski's stain gives the best results) there may be made visible within 
the cell a nucleus {a), and at the same time it may be recognized that the flagellum is 
continued as a border along the outer edge of the undulating membrane {e), and takes 
its rise at the posterior end of the animal from a rod-shaped body (b) lying upon the 
protoplasm-body. Rabinowitsch and Kenipner regard this rod-shaped body, which 
stains similarly to the nucleus, as a constituent of the nucleus separated in space from 
tlie vesicular chromatin-framework, and designate it the nucleolus. Likewise, Plim- 



FiG. ^Wi.— Trypanosoma (herpetomonas) saimiinis mxirium in different stages of development. 
(After A. von Wasielewski.) A, Fully developed parasite with nucleus (a), rod-shaped body (&), undulat- 
ing membrane (c), and flagellum (d) ; B, parasite with two nuclei and one rod-shaped body; C, parasite 
with one nucleus and two rod-shaped bodies ; D, division into two parasites; J5, parasite with four nuclei 
and four flagella ; F, daughter-individuals united into a colony. X 1,500. 

77ier and Bradford distinguish a macronucleus and a micronucleus ; but according to wn 
Wasielewski the structure does not lie in the cell-plasma, but in the periplastem, from 
which the flagellum and undulating membrane also proceed. 

As Rabinowitscli and Kempner have shown, the development and multiplication of 
the parasite can best be foUow^ed through the intraperitoneal inoculation of healthy 
white and spotted rats, an increase of the parasite thereby taking place, partly in the 




684 



THE ANIMAL PARASITES. 



peritoneal cavity and partly iu the blood. According to the reports of these observers, 
multiplication takes place partly through the longitudinal and transverse division of 
flagellated individuals, and partly through the segmentation of larger forms having no 
flagella, the division of the cell being introduced by the division of the nucleus desig- 
nated by them as the chromatin framework, while new nucleoli are constricted otf from 
the chromatin mass. According to von Wasielewski, the nucleus {B) sometimes divides 
first, at other times the rod-shaped flagellum-root (C); and the cells divide sometimes 
when containing two nuclei {D), at other times onl}^ after the formation of several nuclei 
and flagellum-roots {E, F), so that the flagellates during the process of constriction re- 
main united together in a colony for some length of time, 

Plimmer and Bradford claim to have seen in the case of Trypanosoma Brucii also 
conjugation processes with subsequent division ; but this has not been confirmed by 
other investigators. 

The trypanosomata of marmots, cattle, horses, birds, and fishes are similar to the 
trypanosoma of the rat, but according to Rabinoimtsch and Kempner are separate species, 
and the animals named are not susceptible to the trypanosoma of the rat. The trypa- 
nosoma of rat's blood has a pointed posterior end, the Trypanosoma Brucii which causes 
the tsetse disease has a blunt conical posterior end. The trypanosoma of the surra-dis- 
ease of India is probably identical with the latter. 

According to experimental investigations by Rahinowitscli and Kempner, the infec- 
tion of rats is brought about through the bite of diseased rats or by means of fleas ; an 
infection through the intestine does not take place. 



Literature. 

(Amcebw.) 
Behla: Die Amoben, Berlin, 1898 (Lit.). 

Celli u. Fiocca: Beitr. z. Amobenforschung. Cbl. f. Bakt., xvi., 1894. 
Councilman and Lafleur: Amoebic Dysentery. Johns Hopkins Hosp. Rep., ii., Balti- 
more, 1891. 

Cramer: Amobendysenterie. Cbl. f. allg. Path., vii., 1896 (Lit.). 
Dock : Amoeba coli in Dysentery. Daniel's Texas Med. Journ. , 1896 
Doria: Protozoen bei der Endometritis chron. glandularis. Arch. f. Gyn.,47Bd., 
1894. 

Epstein: Monocercomonas horn. u. Amoeba coli bei Kinderdiarrhoen. Prag. med. 
Woch., 1893. 

Feinberg": Unterscheid. v. Amoben u. Korperzellen. Fortschr. d. Med., 1899. 
Gilchrist: Protozoan Infection. Johns Hopkins Hosp. Rep., 1896. 
Harris: Amoebic Dysentery. Am. Journ. of the Med. Sc., 1898. 
Janowski: Aetiologie d. Dysenteric. Cbl. f. Bakt., xxi., 1897. 

Kartulis: Zur Aetiologie der Leberabscesse. Cbl. f. Bakt., ii., 1887; Patliogenese der 
Dysenterieamoben. lb., ix., 1891; Pathogene Protozoen. Zeitschr, f. Hyg.,xiii., 
1893. 

Kovacs: Beobacht. lib. Amobendysenterie. Zeitschr. f. Hyg., xiii., 1892. 
Kruse u Pasquale Unters. lib. Dysenteric u. Leberabscess, Zeitschr. f. Hvg., xvi., 
1894. 

V. Leyden u. Schaudinn- Leydenia gemmipara (in Ascitesfliissigkeit beobaclitete 

Amobe). Sitzber. d. K. Akad. d. Wiss., Berlin, 1896. 
Losch: Massenhafte Entwickelung von ximoben im Dickdarm. Virch. Arch., 65 Bd., 

1875. 

Lowit; Die Leukamie als Protozoeninfection, Wiesbaden, 1900; Specif. Farbung d. 
Hamamoba leucsemiae magna. Beitr. v. Ziegler, xxviii., 1900; Weitere Beobach 
tungen liber die Parasiten der Leukamie. Zeitschr. f. Heilk., xxi., 1900. 

Iiutz: Zur Kenntniss der Amobenenteritis. Cbl. f. Bakt., x., 1891. 

Massiutin: Ueber die Amoben als Parasiten des Dickdarms. Cbl. f. Bakt., vi. 1889. 

Mereschowsky : Arch. f. mikr. Anat., xvi., 1878. 

Osier: Ueber die bei Dysenteric vorhandene Amobe. Cbl. f. Bakt., vii., 1890. 
Pfeiffer: Die Protozoen als Krankheitserreger, Jena, 1895. 
Posner: Amoben im Harn. Berl. klin. Woch., 1893. 
duincke: Protozoenenteritis. Berl. klin. Woch., 1899. 
Quincke u. Koos: Amobenenteritis. Berl. klin. Woch., 1893. 
S.OOS: Zur Kenntn. d. Amobenenteritis. Arch. f. exp. Path., xxxiii., 1894. 
Sclmeidemiihr Die Protozoen als Krankheitserreger, Leipzig, 1898. 
Schuberg: Die parasitischon Amoben des menschl. Darms. Cbl. f. Bakt., xiii., 1898 
(Lit.). 



INFUSORIA. 



685 



Tajardo: Amobenenteritis und Hepatitis. Cbl. f. Bakt., xix., 1896. 

Tenoglia: Entero-colite paramoeba coli. Arch. ital. de biol., xiv., 1890. 

Tlirk: Ueber die Hamamoben Lowit's. Verb. d. Congr. f inn. Med., Wiesbaden, 1900. 

Wesener: Unsere gegenw. Kenntn. iiber Dysenterie. Cbl, f. allg. Path., iii., 1892. 

(Infusoria,) 

Bruce: Report on the Tse.se Fly Disease, Ubomobo, 1895, 1896. 

Danilewsky: Zur Parasitologie des Blutes. Biol. Cbl., v., 1885-86; La parasitologic 

du sang, Charkolf, 1889. 
Dock: Trichomonas as a Parasite of Man. Amer. Journ. of Med. Sc., 1896 (Lit.). 
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Zur Aetiologie d. Masern, Pocken, Scharlach, Syphilis (Protoplasmakorper im 

Bliite imd in Pockenpusteln). Cbl. f. Bakt., xii., 1892. 
Eberlein: Infusorien im Wiederkauermagen (kommen normal vor). Cbl. f. Bakt., 

XX., 1896. 

Ehrenberg : Die Infusionsthierclien, Leipzig, 1838. 

Francis : An Experimental Investigation of Trypanosoma Lewisii. Bull. U. S. Hy- 
gienic Lab. No. 11, 1903. 

Grassi: Protistes endoparasites. Arch. ital. debiol.. ii. , iii., 1882-83. 

Grassi, B., ii. Schewiakofif: Megastoma entericum. Zeitschr. f. wiss. Zool., xlvi., 
1888. 

Grimm: Leberabscess u. Lungenabscess mit Infusorien. Langenbeck's Arch., 48 Bd., 
1894. 

Hausmann: Die Parasiten der weibliclien Geschlechtsorgane, Berlin, 1870. 
Hansen: Infusorien im Magen bei Carcin. ventriculi. Deut. Arch. f. klin. Med., 59 
Bd.,1898. 

Jakoby u. Schaudinn: Neue Infusorien im Darm. Cbl. f. Bakt., xxv., 1899. 
Janowski: Flagellaten i. d. Faeces. Zeitschr. f. klin. Med., 31 Bd., 1896; Balantidium 

coli im Stuhl. lb., 32 Bd., 1897 (Lit.). 
Koch.: Reiseberichte iiber Rinderpest, Bubonenpest, Tsetse- oder Surrakrankheit, 

Texastieber, tropische Malaria, Schwarzwasserfieber, Berlin, 1898. 
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1855. 

liambl: Cercomonas et Echinococcus in hepate hominis. Russ. med. Bericht, 1874. 
Lang: Protozoa, Jena, 1901. 

Laveran: Des tryjDanosomes parasites du sang. Arch, de med. exp., iv., 1892. 
Lindner: Erzeug. v. Hautkrankheiten durch e. Protozoenart. Monatsh f. prakt. 

Derm., xvi., 1893. 
Malmsten: Ueber Balantidium coli. Virch. Arch., 12 Bd., 1857. 
Marchand: Ueber Trichomonas intest. Virch. Arch., 64 Bd. ; Trichomonas im Ham 

eines Mamies. Cbl. f. Bakt., xv., 1894. 
May: Cercomonas coli hominis. Deut. Arch. f. klin. Med., 49 Bd., 1892. 
Miura : Trichomonas vaginalis im Urin eines Mannes. Cbl. f . Bakt. , xvi. , 1894. 
Moritz u. Holzl: Megastoma entericum. Miinch. med. Woch., 1892. 
Motter: Zur Kenutniss des Balantidium coli. Inaug.-Diss., Kiel, 1891. 
Musgrave and Williamson : Trypanosomiasis of Halser in the Philippine Islands, 

U, S. Govt. Lab. Rep., 1903. 
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Perroncito: Ueber die Einkapselung des Megastoma intest. Cbl. f. Bakt., ii., 1887. 
Plimmer u. Bradford: Morphologic d. Tsetseparasiten. Cbl. f. Bakt., xxvi., 1899. 
Rabinowitsch u. Kempner: Rattentrypanosomen. Zeitschr. f. Hyg., 30 Bd., 1899 

(Lit.). 

Rattig: Ueber Parasiten des Froschblutes. Inaug.-Diss., Berlin, 1875. 
Rieck: Sporozoen als Kranklieitserreger bei Thieren. Deut. Zeitschr. f. Thiermed., 
xiv., 1889. 

Roos: Ueber Infusoriendiarrhoe (Megastoma entericum, Trichomonas intestinalis, Cer- 
comonas hominis, Cercomonas coli u. A.). Deut. Arch. f. klin. Med., 50 Bd., 1893. 

Rouget: Trypanosome des mammiferes. Ann. de ITnst. Pasteur, 1896. 

Ruge: Ueb.'d. deutsche Proteosoma (bei Sperlingen). Cbl. f. Bakt., xxix., 1901. 

Schmidt: Trichomonas im Auswurf. Mimch. med. Woch., 1896. 

Sievers: Balantidium coli und Megastoma entericum. Zeitschr. f. klin. Med., 30 Bd., 
1896; Arch, f, Verdauungskrankh., v., 1900. 

Stein: Der Organismiis der Infusorien, Leipzig, 1867-78. 

Stieda: Ueber Balantidium. Virch. Arch., 35 Bd., 1866. 

Streng: Infusorien im Sputum bei Lungengangran. Fortschr. d. Med., x., 1898. 
Wasielewski u. Senn: Flagellaten d. Rattenblutes. Zeitschr. f. Hyg., 33 Bd., 1900. 



THE ANIMAL PARASITES. 



Wittich: Spirillen im Blutc von llain.stern. Cbl. f. d. med. Wiss., 1881. 
Zenker: Cercomonas iiitestinalis. Deut. Zeitschr. f. prakt. Med., 1879. 

§ 181. Of the Sporozoa occnrriug as parasites in man and in the 
mammals, tlie coccidia are to be mentioned first. In their young state 
they exist as non -encapsulated inhabitants of epithelial cells, particulai ly 
in those of the intestinal canal and its adnexa, the liver especially, and 




Fig. 520.— Section through the wall of a dilated bile-duct, filled with coccidia and lined with papillary" 
proliferations. From a rabbit's liver that was studded with coccidia nodules (Miillers fluid, hasmatoxylin, 
eosin). a, Connective tissue; &. branchins: papillary proliferations covered with epithelium; c. coccidia. 
X 23. 

more rarely in those of the organs of excretion. Some of the mature 
forms surround themselves with a capsule and become changed into 
round or oval permanent cysts or oocysts (Schaudinn), which leave their 
resting-place and usually also their host, and under certain conditions 
form sickle-shaped sporozoites through the repeated division of their 
cell body {sporogony) . Through the taking- up of sporozoite-containing 
oocysts into a new host there is produced an infection of the latter, in 
that the sporozoites are set free and seek out epithelial cells for their 
further development. 

Besides this form of multix)lication there occurs within the infected 
organ also a reproduction by schizogony — that is, there are developed 
from mature but non-encysted individuals, by meaiis of segmentation, 

a large number of new sickle -shaped individ- 
uals, the so-called merozoites, which seek out 
epithelial cells, and develop further in the 
same. 

Coccidium oviforme (Fig. 521) is a para- 
site of the intestine and biliary passages, 
occurring especially in rabbits. Kiinstler 
and Pitres found similar coccidia in man in 
a j)leiiritic exudate. Podwyssozki claims to 
have observed them in the human liver. 

In the liver of rabbits the invasion of 
coccidia leads to the formation of white 
nodules which may reach the size of a hazel- 
nut, and are designated as coccidia -iiodules. 
These nodules contain a ^oft. white, or yel- 
lowish-white mass, and consist essentially of 




Fig. 360.— Coccidia from the biliary 
duct of the rabbit's liver (Fig. 520), 
showing different stages of develop- 
ment iMiiUer's fluid,"haematoxylin). 
a, b. Small, coarsely granular young 
forms ; c, d, large forms with darkly 
staining peripheral granules ; e, f , g, 
/j, oval, encapsulated forms, the pro- 
toplasm of whicli— partly coarsely 
granular and partly fine— fills up only 
a portion of the capsule. X 400. 



EPITHELIOMA CONTAGIOSUM. 



687 



dilated bile-passages, the inner surface of which is more or less richly 
furnished with papillary growths (Fig. 520), and whose lumen contains 
great numbers of coccidia. 

The coccidia occur in the bile-passages partly in the form of non-encap- 
sulated protoplasmic structures, and partly in the form of encapsulated 
bodies. The smallest coccidia, which are regarded as the younger forms, 
exhibit a coarsely granular protoplasmic structure (Fig. 521, a, b), 
within which a nucleus (a) may occasionally be demonstrated. The 
larger forms exhibit on their outer surfaces regularly arranged granules 
(c, d), which stain intensely with hsematoxylin. The encapsulated forms 
occur as oval, doubly contoured, clear bodies (e, f, g, li) within which 
lies a variously shaped mass exhibiting also various forms of granulation, 
but never entirely filling up the space within the capsule. 

To the coccidia belong probably also those parasites which occur in 
the epidermis of man and form there peculiar growths known as epithe- 
lioma contagiosum (Fig. 522). In its fully developed condition the 
growth consists of a small nodule, about the size of a pea or larger, 
which is elevated above the surface of the skin, shows a small groove in 
its centre, and possesses a waxy lustre. 

On section there may be seen a lobulated epithelial growth (Fig. 522, 
d), with a central cavity opening externally {g), thus forming a growth 
resembling a gland; and it has been many times mistaken for a hyper- 
trophic sebaceous gland. It therefore represents an independent new- 
formation of epithelium due to a parasite. The parasites develop inside 
of the epithelial cells of the lobulated growth {e), but are pressed by the 



Fig. 532.— Epithelioma contagiosum. Section tbrougli greatest diameter (Miiller's fluid, haBmatoxylin). 
a. Epidermis ; Z), connective tissue ; c, sebaceous gland ; d, gland-like epithelial proliferations ; e, para- 
sites ; /, horny cells mingled with parasites ; (/, duct filled with homy epithelium and parasites. X 13. 

growth of the adjacent epithelium toward the central cavity of the new- 
formation (/), and lie there in a mesh work of desquamated and horny 
epithelial cells. 

The earliest stages of development of the parasites occur in the epi- 
thelial cells as small protoplasmic bodies (Fig. 523, a, h), which can be 
distinguished from the cell -protoplasm only with difficulty ; occasionally 
they contain in their interior small, distinct granules, and are therefore 
more evident. Later they increase in size, and finally fill up completely 
the epithelial cell (c, d, e), pressing the nucleus to one side. At the 
same time the granules within the cell (c) increase, and grow to larger 
bodies, so that the parasite finally becomes divided into a greater or less 
number of finely granidar structures {d, f) lying in a finely granular 




688 



THE ANIMAL PARASITES. 



network. The nucleus of the 
epithelial cell is destroyed during 
this time. 

The epithelial cells which en- 
close parasites develop early a 
distinct membrane, which be- 
comes more and more clearly 
defined, and surrounds the para- 
site. The parasites which are 
expelled from the cells form 
oval bodies which appear en- 
closed in a capsule and present a 
homogeneous appearance. They 
stain deeply with hsematoxylin. 

The contagious epitheliomata 
may appear in great numbers in 
one and the same individual, 
and several persons living to- 
gether may be either simultaneously or successively attacked. The 
spread of the disease is therefore referred to a contagion. 

Our knowledge of the significance of the so-called Miescher's sacs 
is still incomplete. They are tube-shaped structures which are not 
infrequently found in the muscles of the hog (Fig. 524, a, b), cattle, 
sheep (especially in the oesophagus), and mice. They vary in size, and 
lie within the muscle-fibres. In mature parasites the contents of the 
tubes are differentiated into single segments defined by a membrane 
(Fig. 524), which enclose spherical (c), kidney -shaped, or sickle-shaped 
bodies. The parasite is classed with the Sarcosporidia. The separate 
segments are designated sporocysts or sporoblasts, since within these the 
round or sickle-shaped spores {Bainey^s bodies) arise. From the latter, 




Fig. 523.— Parasites of Epithelioma eontagiosum in va- 
rious stages of development, lying inside epithelial cells 
(Miiller's fluid, hteraatoxylin) . a, b, Epithelial cells, en- 
closing a protoplasmic body inside of w^hich lie single 
large granules ; c, epithelial cell almost completely 
flUed with parasites ; d, e, /, parasites completely filling 
the epithelial cells, and divided into numerous separate 
bodies lying in a granular network ; the cell-nucleus 
has been destroyed in /. X about 500. 




Fig. 524.— Miescher's sacs, from swine-muscle, a, b. Muscle cut longitudinally and transversely. X 100. 

. c, Longitudinal section. X 580. 

new Miescher's sacs may develop under favorable conditions (Pfeiffer). 
Ingestion of meat containing sarcosporidia is not dangerous for man. 

As early as 1870 Eimer published observations of the development of coccidia, but 
their life-history has been, accurately determined only in recent years, through the in- 



REPRODUCTION OF COCCIDIA. 



689 



vestigations of R. Pfciffer, Simond, Leger, Schaudinn, Schuherg, SiedlecM, Schneider, von 
W<isielewski, Lahhe, and otliers. LiXhe has recently collected in an excellent manner the 
results of the more recent investigations concerning the sporozoa (Centralbl. f. Bakt., 
Bd. xxvii., xxviii.). 

According to his presentation, the reproduction of coccidia occurs partly through 
sporogony, partly through schizogony. The first method serves for the spreading of in- 
fection and the preservation of the species, the second increases the extent of the infec- 
tion within the infected host. Sporogony is closely connected with a previously occurring 




Fig. 535.— Cycle of development of Coccidium Schuhergi. (After Schaudinn and Luhe). I, Sporo- 
zoite (or merozoite) penetrating into an epithelial cell ; ^, mononuclear schizont in an epithelial cell ; S, 
multinuclear schizont ; U, division of the schizont (schizogony) into numerous merozoites ; 5, macroga- 
mete (female cell) arising from a merozoite ; 6, fully developed macrogamete surrounded by extruded 
chromatin granules; 5a, microgametocyte (male cell) arising from a merozoite; 6a, microgametocyte sur- 
rounded by loosened microgametes (spermatozoa) ; 7, fertilization of the macrogametes by microgametes ; 
8, young oocysts ; 9, oocysts with sporoblasts ; 10, oocysts vt-ith sporocysts, each containing two sporo- 
zoites ; 11, sporozoite. 

copulation which in its course suggests the fertilization of the egg of the metazoa. 
An alternation of generations also takes place. 

The development and reproduction take place in the following manner: In schiz- 
ogony the sickle-shaped germ (Fig. 525, 1) arising as a sporozoite or merozoite develops 
within an epithelial cell into a schizont (:-^) in which there soon takes place a multiplica 
tion of the nucleus (3). There then results (on the second day after the over-feeding of 
sporocysts) a formation of merozoites (4) corresponding in number to the nuclei, and a 
residual body which is left behind after the segmentation. 

The merozoites again seek epithelial cells, and the same development begins anew. 
If the affected organ, as the result of these processes, becomes overcrowded with para- 
sites, there are then formed sexual individuals (Schaudinn). Some of the merozoites 
grow into large cells, the macrogametes {5, 6) or female cells, which when mature throw 
off a portion of their chromatin-substance {6), and either remain naked or surround 
themselves with a capsule, which is provided with a micropyle. At the same time 
other merozoites develop into the male sexual cells or microgametocytes {5a, 6a), the 
nuclei of which divide into many daughter-nuclei. The latter approach the surface of 
the cell, and, surrounded by a certain amount of protoplasm, are constricted off, (6a) 
and then represent the microgametes (corresponding to the spermatozoa of the higher 
animals). The copulation of the microgametes with the macrogametes takes place in a 
manner similar to that of the fertilization of the metazoan egg, in that the microgamete 
penetrates the encapsulated form of macrogamete through the micropyle, and the naked 
form through a certain point which pushes itself outward to form a prominence (7), the 
36 



690 



THE ANIMAL PARASITES. 



coiiceptional protuberance. Sporogony follows the fertilization — that is, the oocyst {8) 
is formed, in which, through the division of the nucleus and protoplasm there arise 
four sporoblasts (9), each of which later produces two sickle-shaped sporozoites {10). 

Sarcosporidia have been observed in manunals (Rosenberg mports tlie finding of 
sarcosporidia in the heart-muscle of a European, luirtnliK a similar finding in the ab- 
dominal muscles of a Sudanese), birds, and reptiles. Their life-history is not yet ade- 
quately known ; and at the present time (LiiJie) a classification of the sarcosporidia can 
not be given. • 

Numerous authors hold the view that other local pathological conditions of the 
tissues in man than those described above may be referred to sporozon, particularly ea?'- 
cinoma, Barier's disease, Fagefs disease, peculiar diseases of the urinary passages, etc. 
It may, however, be remarked that this assumption in part is based upon error, and in 
part has not been absolutely proved by the investigations which have been made up to 
the present time. 

So far as carcinoma is concerned, in spite of the great number of works on the sub- 
ject, so numerous indeed that they can scarcely be perused (cf. § 132), no proof has yet 
been given that protozoa, coccidia in particular, are present within the epithelial pro- 
liferation and are to be regarded as the cause of the same. All the appearances 
described as occurring in carcinoma cells, even the sickle-shaped formations which have 
been thought to be convincing and those provided with a sort of capsule, may be other- 
wise interpreted, and may be explained in part as changed nuclei, in part as altered 
protoplasm of the cancer-cells, in part as cell excretions, and finally in part ^s a product 
of cell-fusion or of the taking up of leucocytes by the cancer cells. 

The disease described by Darier iis 'psorospermose folliculaire vegetante, and referred 
by him to the presence of sporozoa, is very probably only an inflammatory affection of 
the skin characterized by a pathological cornification (keratosis follicularis of von 
Withe), in which little horny plugs and pegs are developed successively in the epithe- 
lium of certain parts of the body, while the cutis shows slight inflammator}^ changes. 
According to Buzzi, Mietlike, Rieck, Krosing, Petersen, and others, the ""corps roiids,''' 
described by Darier as parasites, contain kerotohyalin and eleidin, substances which are 
present in cornified cells but not in gregarinse. 

Pagefs disease is an affection spreading from the nipple, beginning with an eczema- 
like inflammation, and leading to superficial ulceration, and finally ending in a carci- 
nomatous infiltration of the skin. It has been referred by Darier, Wieckham, Malassez, 
and others to the presence of a parasitic sporozoon in the epithelial cells ; but is, how- 
ever, either an eczema arising from other causes, and finally leading to cancer, or else 
is a primary cancer accompanied by inflammatory processes {Ehrhardt), in w^hich pecul 
iar changes take place in the epidermis, particularly swelling of the protoplasm and 
nuclei, with formation of vacuoles, and further proliferative changes, the peculiar ap- 
pearances of which might be mistaken for parasites. 

Pisenti, Silcock, Ete, Bland Sutton, and Jackson Clarke have pointed out the possi- 
bility that the cysts occurring in the descending urinary passages in ureteritis cystica 
are of parasitic origin. Lvbarsch and AscJioff have opposed this view; mn Kahlden has 
upheld it. 

According to Kess and Guilleheau, coccidia may occasion in young cattle diseases of 
the intestine resembling dysentery. 

Ouarnieri ("Ric. suUa patogenesi ed etiol. dell' infez. vaccinica e variolosa," Arch, 
per le Sc. Med., xvi., 1893; "Ulter. ric. Sulla etiol. dell' infez. vaccinica," Pisa, 1896), 
L. Pfeiffer C Die Protozoen als Krankheitserreger," Jena, 1895; " Vaccine-contagium," 
Zeitschr.f. Hyg., 33 Bd., 1896), E. Pf ei ff er C Ziichtung des Vaccine-erregers, " Centralbl. 
f. Bakt., xviii., 1895), and others (cf. " Zelleinschliisse bei Vaccineimpt- 

ungen," Centralbl. f. Bakt., xxi., 1897) consider the small, easily stained bodies, sur- 
rounded by a clear zone, which are found in the epithelium in the early stages of 
variola and vaccinia, to be protozoa. Ouarnieri has designated the supposed parasite 
as Cytoryctes mccinoe. The parasitic nature of these bodies has not yet been demon- 
strated. After Salmon ("Parasites de la vaccine et de la variole," Ann. de Vlnst. Pas- 
teur, 1897) had spoken against such a view, Hiickel ("Die Vaccinekorperchen," 
mn Ziegler, ii., Supplh., Jena, 1898) proved, through exact and carefully conducted 
investigations, that in vaccinia at the point of inoculation into the cornea certain por- 
tions of the epithelial cells undergo especial disease changes, and that from their proto- 
plasm there arise those peculiar structures which have been mistaken for parasites. 



COCCIDIA. EPITHELIOMA MOLLUSCUM. MIESCHER'S SACS. 691 



Literature. 

{Coccidia ; Parasite of Epithelioma Molluscum ^' Miescher^s Sacs.) 

Barrat: The Nature of Psorospermosis. Journ. of Path., iv,, 1896. 
Beck: Molluscum contagiosum. Arch. f. Derm., 37 Bd., 1896. 

Bertram: Zur Kenntn. d. Sarkosporidien. Zool. Jahrb., 1892, ref. Cbl. f. Bakt., xiv,, 
1893. 

Bizzozero u Manfredi: Sul mollusco contagioso. Arch, per le Sc. Med., i., 1876. 
Clarke: Mollusc, coutag. u. Coccid. ovif. Cbl. f. Bakt., xviii., 1895. 
Councilman: A Preliminary Communication on the Etiology of Variola. Jouru. of 
Med. Res., 1903. 

Delepine and Cooper : A Few Facts Concerning Psorospermosis. British Med. Journ. , 
ii., 1893. 

Elmer: Ueber die ei- oder kugelformigen Psorospermien d. Wirbelthiere, Wilrzburg, 
1870. 

Gilclirist: Protozoa, etc. Johns Hopkins Hosp. Rep., i., 1896. 

Grassi: Sur quelques protistes endoparasites. Arch. ital. de biol., ii., iii., 1882, 1883. 
Grunow: Protozoenerkrankung (Coccidien?) des Darms. Arch. f. exp. Path., 45 Bd.,. 
1901. 

Guillebeau: Coccidium oviforme bei der rothen Ruhr des Rindes. Cbl. f. Bakt., xiv., 
1893. 

Hess: Die rothe Ruhr (Coccidienruhr) des Rindes. Schweiz. Arch. f. Thierheilk., 34 
Bd., 1892. 

Israel: Epithelioma foUiculare. Festschr. f. Virchow, Berlin, 1891. 
V. Kahlden: Ueber Ureteritis cystica. Beitr. v. Ziegler, xvi., 1894. 
Kartulis: Pathogene Protozoen. Zeitschr. f. Hyg., xiii., 1893. 

Klebs: Psorospermien im Innern von thierischen Zellen. Virch. Arch., 16 Bd., 1859. 
Kromayer: Histogenese d. Molluscumkorper. Virch. Arch., 132 Bd., 1893. 
Johnson: A New Sporozoan Parasite of Anopheles. Journ. of Med. Res., 1902. 
Labbe: Sporozoa, Das Thierreich, herausgeg. v. d. Deutsch. zool. Ges.. 5 Lief., Berlin, 
1899. 

Lang: Protozoa, Jena, 1901. 

Ltibe: Ergebn. d. neueren Sporozoenforschung. Cbl. f. Bakt., xxvii., xxviii., 1900 
(Lit.). 

Kiinstler et Pitres: Psorospermie trouvee dans une luimeur pleuritique. Journ. de 
Micrographie, 1884. 

Malassez: Sur le psorospermose du foie chez le lapin. Arch, de med. exp., iii., 1891 ; 

Sur les nouvelles psorospermoses chez I'homme. lb., ii., 1890. 
Miescher: Verb. d. Naturforsch. Ges. zu Basel, 1843. 

Neisser: Ueber das Epithelioma contagiosum. Vierteljahrsschr. f. Derm. u. Syph., 
1888; Der gegenwartige Stand der Psorospermosenlehre. Arch. f. Derm. Ergan- 
zungsh., 1892. 

Nocard: Coccidial Tumor from the Small Intestine of the Sheep. Journ. of Path., i., 
1893. 

Pfeiffer, L. : Pathogene Gregarinen. Zeitschr. f. Hyg., iii., iv., v.; Schwarmsporen 
und Dauersporen bei den Coccidieninfectionen und bei Intermittens, Fortschr. d. 
Med., viii., 1890; Die Protozoen als Krankheitserreger, Jena, 1891; Die Zeller- 
krankungen durch Sporozoen, Jena, 1893; Miescher'sche Schlauche mit Mikro-, 
Myxo-, u. Sarkosporidieninhalt. Virch. Arch., 122 Bd., 1890. 

Pfeiffer, E.. : Coccidienkrankheit der Kaninchen, Berlin, 1892. 

Pisenti: Parasitare JSTatur. d. Ureteritis cystica. Cbl. f. allg. Path., 1893. 

Pluymers: Des sacrosporidies. Arch, de med. exp., 1896 (Lit.). 

Podwyssozki : Bedeutung der Coccidien. Cbl. f. Bakt., vi., 1889; Studien tlber Coc- 
cidien. Cbl. f. allg. Path., i., 1890; Entwickelungsgesch. d. Coccidium oviforme, 
Cassel, 1885. 

Rainey: Philos. Transact., T. 147, 1857. 

Rieck: Sporozoen als Krankheitserreger bei Thieren. Zeitschr. f. Thiermed., xiv., 
1889. 

Rixford and Gilchrist: Protozoan Infection. Johns Hopkins Hosp. Rep., i., 1896. 
Rosenberg: Psorospermien im Herzmuskel des Menschen. Zeitschr. f. Hyg., xi., 1892. 
Schaudinn: Der Generationswechsel der Coccidien u. Hamosporidien. Biol. Cbl., vi., 
1899. 

Siedlecki; Cycle evolut. de Adelea ovata. Ann. de I'lnst. Pasteur, 1899. 
Simon; Evolution du coccidium. Ann. de I'lnst. Pasteur, 1897. 



692 



THE ANIMAL PARASITES. 



Sjdbring: Cocciden der Vogel. Cbl. f. Bakt., xxii., 1897. 
Stroebe: Die parasitaren Sporozoen. Cbl. f. allg. Path., 1894 (Lit.). 
Thelohan: Les mj'xosporidies, ref. Cbl. f. Bakt., xix., 1896. 

Thomas: Bone Tumor SuiTOundino; Encysted Coccidia. Report of the Boston Citj 
Hosp., 1899. 

Tordk u Tommasoli: Ucb. d. Wesen d. Ei3ithelioma molluscum. Cbl. f. Bakt., viii., 

1890. 

Tyzzer; Coccidium Infection of the Tiabbit's Liver. Journ. of Med. Res., 1902. 
V, Wasielewski : Sporozoenkunde, Jena, 1896. 

White and Robey: Molluscum contagiosum. Journ. of Med. Res., 1902. 
Wolters: Conjugation u. Sporozoenbildunir bei Gregarinen. Arch. f. mikr. Anat., 37 
Bd., 1891. 

For literature concerning cancer parasites, see § 122. 

(Da rier's Disease ; Paget' s Disease.) 

Boeck: Tier Falle von Darier'scher Krankheit. Arch. f. Derm., xxiii., 1891. 
Darier: De la psorospermos folliculaire ve2:etante. Ann. de Derm., x., 1889. 
Ehrhardt: UeberTaget's Krankheit. Zeitschr. f. Chir., 54 Bd., 1899. 
Jarisch: Darier'sche Krankheit. Arch. f. Derm., xxxi., 1895. 
Karg: Das Carcinom. Zeitschr. f. Chir., 84 Bd. 

Kroesing: Zur Kenntn. d. Darier'schen Dermatosis. Monatsh. f. prakt. Derm., xv,, 
1892. 

Lindt: Ueber Paget's Krankheit, Basel, 1895 (Lit.). 

Mourek: Beitr. z. Lehre v. d. Dermatosis Darier. Arch. f. Derm., xxvii., 1894. 
Pawlow: Psorospermose follicul. vesetante Darier. Arch. f. Derm. Erganzungsh., 
1893. 

Petersen: Ueber die sog. Psorospermien d, Darier'schen Krankheit. Cbl. f. Bakt., 
xiv.. 1893. 

Stroebe: Die parasitaren Sporozoen. Cbl. f. allg. Path., v., 1894 (Lit.). 

Tdrok: Die neueren Arbeiten iiber Psorospermien d. Haut. Monatsh. f. prakt. Derm., 

XV., 1892; Paget 'sche Krankheit. lb., xvi., 1893. 
Wickham: Maladie de Paget du mamelon. Arch, de med. exp., ii., 1890. 

§ 182. Through the in\'estigations of Laveran, Marchiafava, Celli, 
Cxolgi, and others it has been demonstrated beyond doubt that maJaria is 
caused by j;«r«,s?Y^6' belonging to the Protistee, which are usually classed 
together under the name Plasmodium malarise (introduced by Mar- 
chiafava and Celli). They are also frequently designated hsemosporidia. 
The parasites are found in the blood of malarial patients in different 
forms, usually enclosed in cells; and, according to the observations of 
Golgi, Celli, Marchiafava, and others, a definite relation can be demon- 
strated between the number and the stage of the development of the 
parasite and the attacks of fever. The parasites pass through different 
stages of development in the interval between the attacks of fever, these 
stages, according to the authors mentioned, differing in fehris quaHanaj 
fehris tertiana, and fehris quotidiana. At the same time the parasites of 
the different forms of fever exhibit certain differences in their physio- 
logical characteristics. Supported by these facts, there may therefore be 
distinguished in man different species of the malarial Plasmodium. In 
its narrower sense the designation Plasmodium malarice is used only with 
reference to the parasites of quartan and vernal tertian fevers. The para- 
site of festivo- autumnal or pernicious malarial fever, because of its active 
movements, is called Plasmodium vivax (Grassi and Feletti) ; that of quoti- 
dian fever, which also occurs in the autumn, is designated Plasmodium 
prcecox. 

The development and increase of the plasmodia take place within the 
red blood-corpuscles, in which, first of all, small, colorless amoeboid 
bodies (Fig. 526, a) appear. In quartan fever the further development 
of the parasite proceeds by an enlargement of the small amoeboid forms 



MALARIA. 



693 



(Pig. 526, ff , 1), c, d, e), so that the red cell becomes more and more tilled 
up by the parasite. At the same time pigment-granules, which are 




Fig. 52&.—Plas)m)cUuui malaricE of quartan fever, in different stages of development. (After Golgi.) 
a. Red blood-cell with a small non-pigmented Plasmodium ; b, c, d, e, pigmented Plasmodia of varying 
size, inside the red blood-cells; /, Plasmodium in beginning segmentation, with centrally placed pigment; 
f/, segmented Plasmodium ; h, Plasmodium divided into separate spherules ; i, k, two differently-shaped, 
free Plasmodia (sexual individuals). 

formed from the substance of the red cell, appear within the bodies of 
the Plasmodia. When the plasmodia have attained a certain size, the 
pigment-granules move toward the centre, while at the same time a 
radiating cleavage sets in, so that daisy-like figures {'^ rosettes^') (/, g) 
are formed, which consist of a pigmented centre and non-pigmented, ra- 
diating club-shaped i)etals. Later the clubs become detached from the 
central mass of pigment and take on a circular form ( li). 

According to Golgi the development and division of the plasmodia of 
quartan fever require three days for their completion, and the attacks 
of fever coincide with the division of the plasmodia. The red cells occu- 
pied by the parasites are destroyed ; the young plasmodia j ust formed by 
division penetrate again into blood-corpuscles, and the cycle of develop- 
ment begins anew. The pigment-granules formed by the plasmodia are 
taken out of the circulating blood partly free and partly enclosed in cells, 
and deposited in different organs, particularly^ in the spleen, liver, and 
bone-marrow. 

In febris tertiana ( vernal tertian) the cycle of development is completed 
in two days (Golgi). The plasmodia developing within the red cells 
(Fig. 527, ar-d) show much 
livelier motion and lead much 
more quickly to a decoloriza- 
tion of the red blood-corpus- 
cles than those of quartan 
fever, so that the red cells be- 
come decolorized on the first 
day after the fever, while the 
Plasmodia are still small. The 
protoplasm of the plasmodia of 
tertian fever is also more del- 
icate and less sharply con- 
toured and the i)igment-gran- 
ules are smaller. In its division 
each Plasmodium splits up in- 
to from fifteen to twenty new 
cells (e), while the parasite of 
quartan fever forms only from six to twelve. Finally, the red blood- 
cells in quartan fever are mostly crenated, Avhile in tertian fever they 




Fig. o27. —Plasmodium malarke of a vernal tertian, 
showing different stages of development. (After Golgi.) 
rt. First stages of development ; b, c, enlarged Plasmodia 
with pseudopodia : rt, Plasmodia before sporulation, the red 
blood-cell decolorized ; e, sporulation ; /, free parasite 
with flagellum (microgametocyte). 



694 



THE ANIMAL PARASITES. 



retain their shape. According to Celli and Marchiafava, sporulation 
not infrequently occurs prematurely, from five to ten spores arising 
within a red corpuscle. 

The parasite of cestivo-autimmal or pernicious malaria differs from the 
hiemosporidia of the vernal fevers, particularly in the fact that it is much 
smaller (Fig. 528, a, h, c, d) and executes lively movements within the 
red cells. It completes its life- cycle in forty -eight hours. During the 
stage of multiplication the parasite collects in the internal organs, so 
that the division-figures (f?) must be sought in the spleen, liver, bone- 
marrow, and brain (where they are present in great numbers). Some of 
the infected red cells become crenated and prickly, and of a brassy color 
(Marchiafava, Celli) ; they die prematurely, and blood-cells, which con- 
tain no parasites, are also destroyed. The attacks of fever can in the 
case of autumnal tertian fever become so prolonged that they pass into 
one another, and the condition thereby assumes the character of a suh- 
continuous or continuous fever. 

The parasite of the true cestivo-atitiimnal quotidian fever is still smaller 
than that of the autumnal tertian, completes its development in twenty - 
four hours, and produces but little pigment. According to Marchiafa\'a 
and Celli there also occurs a quotidian parasite very similar to the latter, 
but producing no pigment at all. 

According to Celli, Marchiafava, and Bigiiami, nuclear bodies may be 
demonstrated, during certain stages of development, in the protoplasm 
of all the endoglobular forms of malarial hsematozoa. According to 
Ziemann, in sporulation there first occurs a division of the chromatin into 
small clumps, and then later the division of the cell-body, so that every 
clump of chromatin is surrounded by a zone of protoplasm. 

Besides the forms of develoj)ment already described which lead to an 
intracellular increase of the plasmodia through scliizogony, there occur 
particularly extraglobular, in part also endoglobular, round and oval, 
sickle- or crescent-shaped structures (Figs. 526, i, Ic ; 528, e, /), as well 
as round bodies with flagella (Figs. 527, /; 528, g), which also contain 
a nucleus and pigment. The crescent forms occur particularly in the 



First through the investigations of Manson, Bignami, Boss, and Mac- 
Callum, to which were later added those of Grassi, Bastianelli, Bignami, 
Celli, Laveran, Koch, Schaudinn, and others, it was shown that the 
crescents, the oval bodies, the spherical bodies, or spheres, as well as the 




pernicious (gestivo- autumnal 
tertian) fever (Fig. 528, e, / ). 
Celli regards them as a diag- 
nostic feature of this form of 
fever ; and Ziemann also holds 
that typical crescents are not 
formed in the other varieties 
of malaria. 



Fig. Plasmodium vivax of autumnal tertian, show- 
ing different stages of development. (After Celli and San- 
lelice.) a. First stages of development ; ?j, Plasmodia with 
pseudopodia ; c, round Plasmodium with pigment, before 
segmentation; (/, sporulation; e, intraglobular crescent; 
/, free Plasmodia (sexual cells). 



d 



e 



The last-named forms La- 
veran had already described 
as structures belonging to the 
cycle of development of the 
Plasmodia, while Golgi, Can- 
alis, Celli, Marchiafava, Big- 
nami, Bastianelli, Ziemann, 
and others regarded them as 
sterile vegetation - forms. 



MALARIA. 



695 



flagellated bodies known as polymUus, are intended for the reproduetion of 
the parasites by copulation. Tlie flagel la -producing hyaline spheres aris- 
ing from the crescents are male sexual individuals or microgametocytes, 
and the flagella developing from them, in whose formation the chro- 




FlG. r)2<». 



Fig. 530. 



Fig. 529.— Anop/ie/esc lavigcr. (After Meigen, loc. ext.) X i. To the right a wing at higher mag- 
niflcation. 

Fig. 530.— Ookinete of human pernicious malaria (a^stivo-autumnal tertian) in tlie intestinal wall of a 
mosquito. (After Grassi. ) 



matin of the cell takes an essential part (Sacharoif), have the signifi- 
cance of seminal cells, spermatozoa, or microganietes ; while the non-fiag- 
ellated spheres arising from the grannlar crescents have the significance 
of female sexual cells or maerogametes. The crescents leading to the for- 
mation of the sexual cells appear only after the infection has lasted for 
several days. In the chroni(^ cachexia following malaria the forms lead- 
ing to schizogony are absent, and the crescents alone are present. 

The copida.tion of the )n(dari<d parasites of man takes place norjnally in 
the stomach of the mosquito, in diftci'cnt species of Anopheles (Fig. 529), 
which take np the malarial parasites during the sncking of blood from 
malarial patients. 

The copula arising from the nnion of the macrogamete and micro- 
gamete is designated odkinete (Schandinn), a long, motile structure 
(described earlier as vermiculns by Danielewsky) which penetrates into 
the stomach-wall of the mosquito (Fig. 530), where through the forma- 
tion of a capsule it becomes the oocyst. The latter then enlarges, and 
forms numei'ous daughter -luiclei, and then sporoblasts, which break up 
into the sporozoites (Fig. 531) and the residual body. 

The sporozoites, which ai'e formed in enormous numbers, pass into 
the body-caAnty after the rupture of the oocyst, and collect principally 
in the salivary glands, and through the bite of the infected mosquito are 
again transnutted to man, in whose blood they multiply within the red 
blood -cells through schizogony. 

The pathogenic significance of the malarial plasmodia rests in the first 
place upon the destruction of red blood-cells. In the pernicious form 
this may be so extensive that h hemoglobinuria may take place. The 
melanotic pigment formed in the parasite is a pi'oduct of the vital activ- 
ity of the parasites. In addition, as the result of the destruction of 
haemoglobin, there occur deposits of hiemosiderin in the bone-marrow, 
spleen, liver, and occasionally also in the kidneys. The massing of the 
parasites of pernicious malaria in the cerebral capillaries may cause cir- 
culatory disturbances Avith the occurrence of numerous Inemorrhages, 



69(3 



THE ANIMAL PARASITES. 



and consequent severe cei-ebral symptoms (perniciosa comatosa, soporosa, 
apoplectica, meningitica ) . 

As the result of the retention of pigment-containing malarial parasites 
and the deposit of the products of blood-destruction, there occurs a 

marked swelling of the spleen associ- 
ated with hj^pergemia, followed in part 
by tissue- degenerations and in part by 
tissue-proliferations. 

After a long duration of the process 
the spleen may become markedly en- 
larged, i^igmented, and greatly changed 
in structure. Likewise, in the liver 
there may be found iu part degenera- 
tions and x>igmentations, and in part 
also indurative proliferations. 

Certain varieties of the plasniodium 
correspond to the individual types of 
fever, as given above, but it must be 
noted that the fever-forms known as 
quotidian, subcontinuous, and continu- 
, . , , 1 . , n , ous (^'c'om/to/rt^'), ui^iv^ also arise through 

lana (gestivo-autumnal tertian i, lilled with V t ,t t n^-r^ 

sporozoites. (After Giassi.) the prcscuce lu the blood 01 diiferent 

generations of the plasmodia of tertian 
or quartan fevers, so that daily a portion of the parasites comes to sporu- 
lation. In this way there arise quotidian forms of fe\ er, which must be 
regarded as a double tertian intection (quotidiana triquartanaria). 

It is not yet determined whetlier the malarial i)arasites i^roduce tox- 
ins; such production has been many times assumed, but never d*»mon- 
strated. The recurrences of nialai ial iaxev weeks and months after the 
original infection likewise cannot be explained. The assumi)tion of Golgi 
that the crescents, which may be found in the circulating blood during 
the interval, aid in the production of the recurrence, is opposed by others 
(Celli). According to Plehn basophile granules are found in the red 
cells as long as the infection lasts; when it ceases they disappear. 

The malaria occurring in northern countries corresponds in general 
to the vernal forms of Italy, while the jestivo- autumnal form is found in. 
the tropics. 

Hsemosporidia — that is, sporozoa which live at the cost of the red blood-cells, and 
thereby produce diseases which are to be classed with malaria — occur very frequentlj'- 
in animals. Those of birds are best known {Danileicsky , MacCallum, Boss, Grassi, 
I>ionisi, Celli), and the life-cycles of the ha^mosporidia of the pigeon, owl, and skylark 
have been determined. Labbe distinguishes two genera in birds, Halteridium and Pro- 
teosoma ( Rmnoproteus of Kruse) ; as to the number of undifferentiated species, nothing 
can be said at the present time. Celli obtained from the birds mentioned three well- 
defined species. 

Of the Mammalia, cattle iu particular suffer in different countries (Southern States 
of ]!^orth America, Italy, South Africa, Roumania) from a malaria characterized by 
high fever and haemoglobinuria. In the malaria of cattle known as Texas-fever, Smith 
and Kilbourne found iu the red blood-cells a small, often pear-shaped, and paired para- 
site {Piroplasma bigemiiiiim), whose pathogenic significance they determined through 
the inoculation of healthy cattle Avith blood containing the parasites. They showed 
further that the natural infection takes place through parasitic ticks living upon the 
cattle, the infection being transmitted, not b3' the same tick which takes up the infected 
blood, but only through the generation descending from the same. This mode of in- 
fection was confirmed by Koch in the haemoglobinuria of cattle occurring in German 
East Africa and by Grassi in that occurring in cattle iu Italy. The mode of develop- 
ment of the pi ra2)las??ia in the body of the tick is still unknown ; and it therefore cannot 




Fig. 531.— Oocyst of human pei niciMus ma- 



DEVELOPMENT OF PROTEOSOMA. 



697 



be decided whether the parasite should be classed with the known malaria parasites. 
Against a near relationship with the latter speaks the fact {Luhe) that it increases within 
the red blood-cells by a repeated simple division. According to KoUe, there occurs in 
South Africa, besides Texas-fever, another malarial disease of cattle {Febris malaria- 
formis), which is caused by a similar endoglobular parasite. 

According to Bonome and Gelli haemosporidia also cause malaria in sheep and lambs, 
according to Piana and Oalli- Valerio also in dogs, according to Koch and Kossel also in 
apes, and according to Dionisi in bats ; but the life-history of all these parasites is 
unknow^n. 

Danilewsky and Gelli have described haemosporidia in the frog, and the latter ob- 
server determined also the development of the parasite in the blood. 

Whether the malarial parasites of man can be transmitted to animals, or whether 
the malaria of animals can lead to an infection of man through the medium of mos- 
quitos, is not decided with certainty, but appears improbable. The plasmodia of the 
bat most closely resemble those of man, yet attempts at inoculation made by Dionisi 
gave no positive results. It may therefore be assumed that malaria would die out in 
a given region, either when all susceptible anopheles w^ere killed, or all infected human 
individuals healed or protected from mosquito bites. 

The malarial plasmodia are stained best by the Romanowski stain, which differen- 
tiates the nucleus. 

The view that mosquitos were concerned in the distribution of malaria is very 
old, and has obtained in Italy since Roman times. Koch found it held as a popular belief 
also among negroes. In recent times Manson (1896) and Bignami (1896) were the first 
to turn their attention to the problem and to give hypotheses concerning the role played 
by mosquitos in the spread of malaria. Bignami carried out experiments along this 
line, but came to no positive result. Ross was the first (1897-98) to determine the cycle 
of development of the malarial Plasmodium of birds (usually known as proteosoma). 
According to his investigations, the parasites taken up with the blood of the infected 
bird into the intestinal canal 
of mosquitos penetrate into 
the intestinal wall and there 
change into cysts in which in- 
numerable rod-shaped germs 
develop. Becoming free, 
these germs gain entrance in- 
to the salivary glands of the 
mosquitos, and thence into 
the organism of the bird dur- 
ing the act of blood-sucking. 
Ross found the parasites in 
the blood of the infected bird 
in from five to nine days after 
the infection. 

About the same time, 
Grassi found through pains- 
taking observations that the 
distribution of malaria in 
man corresponded to the dis- 
tribution of Anopheles claviger 
{Fabricius) (Fig. 529), and not 
to that of the common mos- 
quito ((7'wto pipiens). Basing 
his experiments upon this 
observation, Bignami suc- 
ceeded in producing malaria 
in healthy men by means of 
the bite of anopheles. Later 
Grassi, in cooperation w^ith 
Bastianelli and Bignami, suc- 
ceeded in determining the 
life -cycle of the malarial par- 
asite. It was then shown 
that several species of ano- 
pheles native in Italy {Anopheles clainger [Fabricius] or Anopheles maculipennis [Meigen], 
Anopheles superpictus, pseudapictvs, bifurcatus) spread the malaria occurring in man, 
while Gulex pipiens is the host of the parasites of bird-malaria. 

The cycle of development of the malaria Plasmodium is as follows : Within the 




Fig. 532.— Cycle of development of Proteosoma. (After Schau- 
dinn and Liibe.) i, Sporozoite (or merozolte) within a red blood- 
corpuscle ; ^, schizont ; 3, schizont with numerous nuclei ; A, schiz- 
ogony, formation of merozoites ; 5, macrogamete (female cell) 
arising from a merozoite ; 6, fully developed macrogamete after ex- 
trusion of the karyosome ; 5a, microgametocyte (male cell) arising 
from a merozoite; 6a, microgametocyte surrounded by loosened 
microgametes (spermatozoa) ; 7, fertilization of the macrogamete ; 
5, ookinete ; 9, oocysts \nt\i sporoblasts ; JO, oocysts with sporozoites ; 
1 7, free sporozoite. 



THE ANIMAL PARASITES. 



blood (of man as well as of birds.) the multiplication takes place first hx scJdzogony . The 
young form of the plasmodia, represented by a small, unpigmented body, grows within 
the red cells (Fig. 08'^. i) into a larger body {J), in whose central portion pigment- 
granules collect. This cell-body kuowi] as ^flnzoid shows in preparation for schizogony 
an increase of nuclei (J), and then divides into a number (varying with the species) of 
sp'>n)< or intr(jZ(iit(s{ 'i) with the abandonment of a pigmented residual body. The mero- 
zoites then seek a red blood-cell and tlie cycle is again begun. 

In sporogoiiy the merozoites develop into sexual individuals, macrogametes (5) and 
niicrogametocytes (Jt/)- When taken up into the stomach by blood-sucking mos- 
quitos, the sexual individuals become ripe for fertilization, the macrogamete by 
throwing off the karyosome {6), the microgametocj^te through the formation of micro- 
gametes (6V^\ Copulation then follows ( r i. From the copula arises the motile ookinete 
{8), which in the wall of the mosquito's intestine becomes the oocyst, in which through 
the division of the nucleus the sporoblasts ( are formed, which in turn break up into 
a large number of sporuzoites (/"), whieli (77), becoming free, collect chiefly in the sali- 
vary glands, and are thence transferred Ijy the bite of the mos(|uito to a new host, in 
whose blood they increase thr(~)Ugh schizogony (7-jK 

Tlie larA'a' of anopheles li\ e chielly in slowly tlowiug water. The eggs of Anopli- 
ih-^ diirir,,r rr(|uire about thirty days at 20 -2.-)' C. for the development of the in- 
sects, and t:ie-e in turn lay eggs when twenty (la} s old. The pupae are resistant to 
dr}-iug. to cold, and to contamination of the water. The mosquitos fly during the 
evening and night, but do not rise very liigh above the level of the earth, and do not 
go very far awa}' from the place of development. According to Grassi. Bignami, and 
BiiKtid niiJ/i . the a-'-ti\'o-aiitumnal parasites will not de"\"elop in anojiheles at a tempera- 
ture of 14 -15 ('.. and grow onl\ slowly at ^O'-^O C. ; at 30' C\ they complete their 
entire development up to the formation of sporozoites in about seven days. 

The literature concerning malarial parasites is extremely rich. The results of the 
latest investigations are given in the publications of Mannabery, ynttaU. Celli, Marchi- 
afu.i-ii. Bigniiini. and Li'Iit isee below). The last-named treats particularl}- of the ques- 
tion of the position of the malarial parasites in the zoological system and their relation 
to the other sporozoa, in particular to the eoccidia. 



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MALARIA. 



699 



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700 



THE ANIMAL PARASITES. 



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Stein: Structur des Paras, der Malaria tertiana. Virch. Arch., 159 Bd., 1900. 
Thayer and Hewetson : 3Ialarial Fevers of Baltimore, Johns Hopkins Press, 1895. 
Wilde: Ergebnisse der Malariaforschung. Miinch. med. Woch., 1901. 
Ziemann: Blutparasiteu bei heimischer u. tropischer Malaria. Cbl. f. Bakt., xx.^ 

1896; Ueber Malaria und andere Blutparasiteu, Jena, 1898. 



II. Vermes (Worms). 

A. Platyhelmixthes (Flat-Woems). 
1. Trematoda, SucTcuig Worms. 

§ 183. The Trematodes or sucling- worms are flat-worms of tougue or 
leaf shape. They possess a clinging apparatus iu the form of ventral 
sucking-cups of varying number, and are sometimes furnished with hooks 
or clasp-like horny projections. The intestinal canal is without an anus, 
and is usually forked. The development takes place either hj the direct 
growth to maturity of the embryos (miracidium) hatching from the eggs, 
or by the method of alternate generation througli the formation of germs 
within the host. The miracidium, or ciliated embryo, penetrates into a 
snail or mussel, and there grows into a genn-sae (sjwroei/st), within which 
there later develops, either directly or after the formation of an inter- 
mediate generation of germ-sacs a swarming generation of cer- 
carice, which are pro^'ided with rudder-like tails. These lose their tails 
and penetrate into a new host (moUusks, arthropods, fish, amphibia\ 
become encapsulated, and attain sexual maturity as soon as they reach 
the final host. The germ-sacs which produce cercari?e are designated 
primary germ-sacs Ammen^^) ; if they fii-st form rediie and then cer- 
carise, they are called secondary germ-sacs ('^ Grossammen^^). 

Distoma hepaticum, or liver-fluke, is a leaf -shaped sucking- worm 
about 28 mm. long and 12 mm. broad (Fig. 533). The cephalic end 
projects like a beak, and bears a small sucking-cuj), in which the mouth 
is placed. Close behind this, on the ventral surface, is a second sucking- 
cup, and between the two lies the sexual orifice. 

The uterus consists of a couA^oluted, globular sac behind the posterior 
sucking-cup. On each side of the hinder part of the body lie the yolk- 
sacs, and between the same are found the testicular canals, which bmnch 
many times. The forked intestinal tract (not visible in Fig. 533) is 
repeatedly branched. 

The eggs (Fig. 534) are oval, 0.13 mm. long and 0.08 mm. broad. In 
water there develops an embryo, the miracidium (Fig. 535, A), with 



TREMATODA. 



701 



cellular germ-balls (a); with the aid of its ciliated coveiing the embryo 
swims about, and seeks out a new host from the family of mollusks 
(^Limnceus minutus). On penetration into the snail the cutaneous layer is 
thrown off, and the miracidium, which possesses an intestine, an excre- 
tion-organ and a brain -ganglion, becomes changed into a sj^orocyst {B), 
in which the intestine and nervous system atrophy, while the cellular 
germ-balls develop further (B, a) and form a second generation of germ- 
sacs, the redice (B, h). The redise {€), which 
possess an intestine (C, a), produce then 
within the same host the cercarice (I)) from 
cells which are loosened from their germ- 
matrix (0, &) ; these abandon the host and 
with the aid of a rudder -like tail swim about 
in the water. With the loss of their tails they 
become encysted upon almost any foreign 
body, and then reach their final host (usually 
through the food), in which they attain sex- 
ual maturity. The sexually mature animal 
inhabits the biliary passages ; more rarely it 
is found in the intestine or inferior vena 
cava. The liver-fluke is rare in man, but 
common in the ruminants. The results of its 
invasion, especially when it is present in 
great numbers, are obstructions and ulcerative 
strictures of the bile -passages, formation of 
biliarv concretions, inflammation of the tis- 





FiG. 533. 



FIG. 534. 



Fig. SSS.—Distoma hepaticum with male and female sexual apparatus. 
Fig. 534.— Eg-gs of Dlstoma hepaticum. (After Leuckart.) X 200. 



(After Leuckart.) X 3.2. 



sues in the neighborhood of the bile-ducts, and hyperplasia of the con- 
nective tissue of the liver with atrophy of the glandular tissue. 

Distoma lanceolatum is only 8-9 mm. long and 2-2.5 mm. broad, is 
lancet-shaped, and the cephalic portion is not especially marked off 
from the body (Fig. 536). 

The skin of the body is smooth. Two irregularly lobed testicles (h) 
lie close behind the ventral sucking-cup, in front of the ovary (o) and 
the uterus (u), the coils of which shine through the transparent body. 
The anterior coils are black with the ripe eggs, the others are rusty red. 
The yellowish -white yolk-sacs (d) lie in the middle of the lateral 
margin. 

The oval eggs are 0. 04 mm. long, and while still in the uterus contain 
an embryo which escapes only after several weeks following the casting- 
off of the eggs. Its metamorphoses are unknown. 

Distoma lanceolatum likewise inhabits the bile -passages, but is very 
rare in man. It is of more frequent occurrence in sheep and cattle. 



702 



THE AXTMAL PARASITES. 



When present only in small numbers, it causes no marked changes; but 
the presence of large numbers may excite inflammation and proliferation 
of the periportal connective tissue. 




Fig. 535.— Development of the liver-fluke. (After Leuckart.) ^i, Miracldium with germ-balls (a) ; B, 
sporocyst with germ-balls (a) and redii^ ib) ; C, redia, with intestine (a) and germ-balls (b) ; D, cercaria 
with mouth (a), abdominal sucking-cup (b), intestine (c), and glands (d). 



Distoma spathulatum (Fig. 537) is a sucking-worm occurring in 
man in Jaj)an and China. It is 10-14 mm. long and 2.5-4 mm. broad. 

The eggs are 0. 02 7-0. 03 mm. long and 0. 015-0. 01 S 
mm. broad. The parasite inhabits usually the bile 
passages and the gall-bladder, but may also gain 
access to the pancreatic duct (Katsurada), and pass 
out into the intestine. When occurring in great 
numbers (Katsurada counted 1,361 in one case) it 
causes an obstruction to the outflow of the bile, and 
often excites a more or less severe inflammation and 
proliferation of connective tissue. 

The parasite is found also in cats and dogs 
(Katsurada). 

Distoma Westermanni (Kerbert), or Distoma 
puhnoMde (Baelz) also occurs in Japan, China, and 
Corea. The worm is 7.5-10 mm. long, 5-7.5 mm. 
broad, egg-shaped, with slightly flattened ventral 
surface. The oval eggs are 0.09 mm. long and 
0.056 mm. broad. The internal organization (Fig. 
538) resembles that of the other trematodes. It 
occurs in man as well as in cats and dogs (Katsu- 
rada). It is found most frequently in the lungs, 
but occurs also in other organs : the pleui^a, brain, 
liver, intestinal wall, peritoneum, orbital cavity, 
eyelid, scrotum, etc. In each case it occupies 
small cavities surrounded by newly formed con- 
nective tissue, and occurs occasionally in pairs. In 
the lung it may be found also in the bronchi, the 
walls of which show inflammatory changes (Katsu- 
rada). Its presence in the lung may give rise to 
haemoptoe and cause death. The number of lung- 




FiG. 536.— D(.sto»ia 
ceolatum. (After Hertwig.) 
8^, Anterior sucking-cup, 
and entrance into the forked 
intestine ; s", p o s t e r i o r 
sucking-cup; /i, testicles 
with vasa deferentia; c, 
cirrus ; t;, uterus ; o, ovary ; 
7, duct of Laurer and shell- 
gland ; d, yolk-stalks and 
duct leading to the shell- 
gland ; u\ water- vessel ; g, 
ganglion. X 8. 



TREMATODA. 



703 



flukes may ruu from twenty to thirty or even higher. Healing of 
the disease is possible after death of the parasite. 

Distoma felineum (Eivolta) or Bistoma sibiricum (Winogradow) is 
a flat, almost transparent sucking- worm, of from 8-18 mm. in length and 
1.5-2.5 mm. broad, which is present in the bile-passages of the cat and 
dog, and in a few countries (Siberia) has been observed in man. Ac- 
cording to Winogradow it is the most common parasite in Tomsk. 
Askanazy recently observed a case in Konigsberg. 

The inflammatory proliferations which the different forms of distoma 
cause in the liver of man, as well as in animals, may be followed by the 
development of carcinoma. 

In Distoma hsematobium or Billiarzia hcematoUa (Fig. 539) the two 
sexes are separate. The mouth and ventral cups lie very close together 
on the tapering anterior extremity. In both sexes the sexual openings 
lie close behind the ventral sucking-cup. The male is 12-14 mm. long. 




FIG. 53T. Fig. 538. 



leiG.bm.—Dutomaf^pathulatum. (After Katsurada.) a. Mouth sucking-cup; ?>, intestine ; c, uterus; 
(i, testicles ; e, yolk-stalks ; /, sperm-pouch ; g, ovarium. X 6. 

Fig. 538.— -Distoma TTesfermaimi, flattened by pressure, in the ventral position. (After Katsurada. i 
a, a„ Mouth and abdominal sucking-cup respectively; i>, intestinal loops; c, testicles; d, ovarium; c, 
yolk-stalks; /, shell-gland; uterus; 7), excretory vessel. X 7.2. 

The body is flat, but in its posterior portion is rolled together to form a 
tube (Fig. 539) which serves for the reception of the female. 

The female is 16-19 mm. long and nearly cylindrical. The eggs are 
an elongated oval (Fig. 540), 0.12 mm. long, and possess a terminal or 
a lateral spine. According to observations by Sonsino, no altneration of 
generations occurs in the development of Distoma hcematobium. The 



70^ 



THE ANIMAL PARASITES. 



part of intermediate host is taken by small Crustacea, into which the 
ciliated embryo, swimming around in water, bores its way to become 
encapsulated in the tissues of its host. It is therefore probable that the 
infection may be transmitted through the drinking of water infected 
with the larvge. 

The worms are found in the trunk and branches of the portal vein, in 
the splenic vein, mesenteric veins, as well as in the vessels of the rectum 
and bladder ; and may pass through the inferior mesenteric vein into the 
hsemorrhoidal and vesical veins, the veins of the ureter and prostate, 
and by chance into the inferior vena cava, and thence into the lungs. 
Their eggs are distributed therefore especially throughout the mucosa 
and submucosa of the ureters, bladder, and rectum, and occasionally also 
in the liver, lungs, kidneys, and prostate. While still within the urinary 
passages the cylindrical embryos (miracidia) covered with fine cilia may 




Fig. 539. Fk;. 540. 



Fift. 539.— ZhVsfoma hcBmatobium. (After Leuckart.) Male and female, the latter lying in the canalis 
gynaecophorus of the former. X 10. 

Fig. 540. — Eggs of Distoma hcematohium. (After Leuckart.) a, Egg with terminal spine; b, egg 
with lateral spine. X 150. 

develop. Kartulis found them also in the skin of the leg and foot, and 
is of the opinion that the infection may take place not only through the 
intestine, but also through the skin. 

The deposit of eggs causes severe inflammations which lead in part to 
tissue -destruction and in part to proliferations of the tissue, which ap- 
pear in the mucous membranes as papillary and polypoid formations. In 
the bladder it may lead to incrustations and formation of concretions, 
and also to the development of fistulous tracts. In the liver the process 
leads to a connective-tissue induration. Following the inflammatory 
process, a development of carcinoma may take place in the bladder, 
seminal vesicles, prostate, and in the skin (Kartulis). 

The parasite is found along the entire eastern coast of Africa, and 
also in Zanzibar, Tunis, Lake I^yassa, in Beyrout, and in Sicily. It is 
most common in Egypt, where about twenty -five per cent, of the native 
population suffer from the disease. 

Literature. 

{Distoma. ) 

Albarran et Bernard: Tumeur epithel. due a la Bilharzia. Arch, de med. exp., 1897. 
Askanazy: Dist. felineum beim Menschen. Cbl. f. Bakt., xxviii., 1900. 
Aschoff: Ein Fall v. Distoma lanceolatum in der menschl. Leber. Virch. Arch., 130 
Bd., 1892. 

Baelz: Einige neue Parasiten des MeEchen. Berl. klin. Wocli., 1883. 



CESTODA. 



705 



Bieliriiiger : Arbeiten z. Entwickelungsgeschichte des Leberegels. Biol. Cbl., viii., 

1888. 

Biermer: Leberdistoma. Schweiz. Zeitschr. f. Heilk., ii., 1863. 

Bilharz: Distomum haematobium u. Verand. d. Harnorgane. Wien, med. Woch., 
1865. 

Bostrdm: Leberdistoma beim Menschen. Deut. Arch. f. klin. Med., xxxiii., 1883. 
Braun; Die Wohnsitze d. endoparasitisclien Trematoden. Cbl. f. Bakt., xiii., 1893; 

Leberdistomen d. Hauskatze. lb., xiv., 1893; Fur d. Menschen neues Distomum. 

lb., XV., 1894. 

Brock; On the Bilharzia Haematobia. Journ. of Path., ii,, 1893. 

Chaker: Etude sur I'hematurie d'Egypte causee par la Bilharzia haematobia, Paris, 
1890. 

Fritsch: Zur Anatomic der Bilharzia haematobia Cobb. Arch. 1 mikr. Anat., xxxi., 
1888. 

Griesing-er : Arch. f. physiol. Heilk., xiii., 1854. 

Kartulis: York, d, Eier des D. haemat. in den Unterleibsorganen. Virch. Arclr., 99 

Bd., 1885; Pathol. Anat. der Bilharzia. lb., 152 Bd., 1898. 
Katsurada: Dist. spathalatum u. D. Westermanni. Beitr. v. Ziegler, xxviii., 1900 

(Lit.). 

Leuckart: Ueber den grossen amerikanischen Leberegel. Cbl. f. Bakt., xi., 1892. 
Loess: Zur Lebensgeschichte der Bilharzia haematobia. Cbl. f. Bakt., xvi., 1894; 

Trematodenfauna Aegyptens. Zool. Jahrb., xii., 1899; Cbl. f. Bakt., xxxiii., 1892. 
Lutz: Zur Lebensgeschichte des Distoma hepaticum. Cbl. f. Bakt., xi., 1892. 
Meinecke : Dist. haematobium in d. Blasenwand. Jahrb. d. Hamb. Krankenanst., v., 

1897. 

Poirier: Contrib. a I'histoire des trematodes, Paris, 1885, and Note sur une nouvelle 
espece de distome parasite de I'homme, le distomum Bathousi. Arch, de zool. exp., 
v., 1887. 

V. Ratz: Leberegel in der Milz der Schafes. Cbl. f. Bakt., xxvi., 1899. 
Riitimeyer : UelDcr Bilharziakrankheit. Mittheil. a. d. Klin. d. Schweiz, Basel, 1894. 
Schaper: Die Leberegelkrankheit der Haussaugethiere. Deut. Zeitschr. f. TlMcrmed., 
XV., 1889. 

Schauinsland • Embryonalentvvickelung der Trematoden. Jen. Zeitschr. f. Naturw., 
xvi., 1883. 

Scheube. Die Krankheiten der warmen Lander, Jena, 1900. 

Sonsino . Discovery of the Life History of Bilharzia Hsematobia. The Lancet, 1893. 

Ward: Trematoda, Ref. Handbook of Med. Sc., 2d ed., 1903. 

Winog-radow : Eine neue Distomaart. Cbl. f. allg. Path., iii., 1892. 

Yamag-iva- Zur Aetiologie der Jackson'schen Epilepsie (Eier von Distoma pulmonale 

im Gehirn). Virch. Arch.. 119 Bd. ; Ueber Lungendistomenkrankheit in Japan. 

lb., 127 Bd., 1892. 

2, Cestoda (^Tapeworms). 

§ 184. Th^tapeworms sure flat- worms devoid of mouth or intestine, which 
increase after the method of alternate generation through the germination 
of a pear-shaped primary head or scolex, and remain united to the latter 
for a long time as a (usually) long, band-shaped colony. The single 
segments of this colony, the sexually active individuals, or proglottides, 
increase in size the more widely they become separated from their place 
of origin by the formation of new members, but outside of this are de- 
void of any outward distinguishing peculiarity. The pear-shaped head 
or scolex, on the other hand, is provided with from two to four suckers, 
and usually also with curved claw-like hooks. With the aid of these 
clinging organs the tapeworms fasten themselves to the intestinal wall 
of their host, which appears to be invariably one of the vertebrate ani- 
mals. The scolices develop from a round embryo having four to six 
hooks, and are found as the so-called "measles'^ in the most diverse or- 
gans, chiefly the parenchymatous ones, from which they later pass by a 
passive migration into the intestine of their future host. 

The tapewo7mis occurring as parasites in man belong to different families 
— the Tceniadce and the Bothriocephalidce. The first occur in man either 
as measles'^ or as tapeworms, the latter only as tapeworms. 
37 



706 



THE ANIMAL PARASITES. 



§ 185. Taenia solium in its fully de\eloped condition possesses a 
length of 2-3 metres. The head (Fig. 541) is of the size of a small pin- 
head, is spherical in form, with rather prominent sucking-cups. The 
crown of the head is not infrequently i^igmented and bears a fairly large 
rostellum with about twenty-six jDlump, close booklets having short root 
processes. Following the head there is a thread-like neck of about an 
inch in length. At a certain distance from the head segmentation begins, 
the first segments being very short, but their length increases with their 
distance from the head (Fig. 512); they become quadratic and finally 
longer than broad. The mature segments appear about 130 cm. behind the 




A. 

Fig. 5il. Fig. 542. Fig. 543, 



Fig. 541.— Head of Tcenia solium with protruding rostellum (carmine, balsam). X 50. 
Fig. 542.— Half-developed and fully matured segments. Natural size. (After Leuckart.) 
Fig. 543.— Two proglottides with uterus. (After Leuckart.) X 2. 

head, although the sexual organs are fully developed in earlier segments. 
The ripe segments (Fig. 513) are, when stretched out, 9-10 mm. long, 
and 6-7 mm. broad, and have rounded corners. The sexual opening is 
situated laterally just behind the middle of the segment. The uterus, 
which is filled with eggs, possesses seven to ten lateral branches which 
are separated from each other by a ^ide interval, and break up into a 
varying number of boughs branching like a tree. 

The parenchyma of the body of mature as well as of immatui-e proglot- 
tides, or tapeworm segments (Fig. 511), is divided into two chief layers, 
the central one being designated the middle layer, the peripheral one as 
the cortical layer. The middle layer contains the sexual apparatus (Fig. 
511, c, d, e, f, g, li, i, Jc, 1, m, n), as well as the water vascular system (a), 
an excretory apparatus which traverses the whole tapeworm from the 
head to the last segment in the form of two canals lying in the lateral 
border of the middle layer. The canals are connected with each other at 
the posterior end of each segment («') and also send out numerous fine, 
subdividing branches into the body-parenchyma. 



CESTODA. 



The sexual apparatm consists of male and female sexual organs, which 
lie close together. A number of small, clear vesicles serve as testicles 
(c), they lie chiefly in the anterior portion of the middle layer The vas 
deferens (e), which is con- 
nected with the testicles by 
the seminal ducts (d), emp- 
ties into a grooved papilla 
situated on the lateral border 
(/t). The coiled end (/, g) 
lies in a muscular bag and 
may be protruded through 
the sexual opening {cirrus). 
The female sexual opening 
lies close behind the male 
orifice in the same sexual 
cloaca. The vagina (i) leads 
thence to the posterior border 
of the segment. Before this 
is reached it widens into the 
seminal vesicle, and behind 
this into the fructifying can- 
al and the so-called "globular body.'^ The germ-preparing organs, 
which must be sought in the immature segments, consist of a double ovary 
(Jc) and a single albumin-gland (?) ; these are sac-like or tubular orgaus 
lying in the posterior portion of the segment and communicating with the 
globular body. The latter is joined to the anteriorly located uterus (n), 
which at the time of sexual maturity forms a straight canal. When the 
eggs enter the uterus from the globular body, in which they pass their 
first stage of development, the above-mentioned lateral branches sprout 
out and become filled with eggs. During this process the remaining sex- 
ual organs disappear. 

The cortical layer of the proglottides is essentially muscular in nature, 
but in addition contains a larger or smaller number of so-called calcareous 
bodies, which are not entirely wanting in the middle layer as well. The 
musculature consists of smooth fibres, which form special groups in the 
suckers of the head. The surface of the tapeworm is covered with a 

clear cuticle, which forms the hooks 
on the heads. 

The eggs in the ovary are thin- 
skinned, pale and yellow, nearly 
globular cells. In the uterus they 
change into yellow balls having a 
thick, more or less opaque shell, 
covered with closely set spicules 
(Fig. 545, a). The latter is often 
surrounded by a second layer, an 
albuminous envelope (&) limited 
by a membrane; and in it there 
are embedded granules (primitive 
vitelline membrane). The diam- 
eter of the eggs, not including the vitelline membrane, is about 0.03 mm. 

The thick-shelled spheres are not undeveloped eggs, but contain an 
embryo with six booklets. An intra-uterine development of the em- 
bryo therefore takes place, the ripe segments are pregnant animals. 




Fig. 544 —Segment of Tcenia solium with fully developed 
sexual apparatus. (After Sommer.) A, Surface view of 
segment; B, border of next anterior segment; C, that of 
next posterior segment; a, longitudinal excretory trunk ; aj, 
transverse anastomosis; if), longitudinal plasma-vessel; c, 
testicular vesicles; d, seminal ducts; e, vas deferens; /, 
cirrus-bag with cirrus ; g, porus genitalis ; K border papilla ; i, 
vagina ; k, ovarium ; Z, albumin-gland ; m, egg-gland, and 
oviduct in front of same ; ri, uterus. X.37. 






FIG. 545. 



Fig. 546. 



Fig. 545. —Eggs of Tcmia solium, b. With primi- 
tive vitelline membrane ; a, without primitive vitel- 
line membrane. (After Leuckart.) X 300. 

Fig. 546.— Cysticercus cellulosae, with fully devel- 
oped head in situ. (After Leuckart.) X 4. 



THE ANIMAL PARASITES. 




The further development of the embryos euclosed in the brownish shells 
takes place ordinarily in a new host. Should they gain access to the 
stomach of a hog, the egg-shell is dissolved, and the embryos, thus set 

free, penetrate into the stomach 
or intestinal wall. Thence they 
pass either by the blood- stream 
or by an active migration 
through the tissues into this or 
that organ. Having reached a 
resting-place, the embryos un- 
dergo various metamorphoses 
' J and become changed inside of 

^ ' two or three months into a cyst 

filled with serum (Fig. 546), the 
inner wall of which shoots forth 
into a bud from which there de- 
velops a new tapeworm head, a 
scolex, as well as a sac enclosing 
the same, a receptaculum scoUcis. 

The cyst containing a tape- 
worm head is known as a 
'* measle or cysticercus cell= 
ulosae. The scolices, when fully 
developed, possess a circle of 
booklets, suckers, a water-vas- 
cular system and numerous cal- 
careous bodies in their body- 
parenchyma. If they gain access 
to the human stomach, the cyst 
is dissolved, and there develops, 
through the formation of seg- 
ments from the scolex (Amme), 
a new chain of proglottides, a 
new Tcenia soliimi. 

The Tcenia solium inhabits the 
small intestine of man, and is ac- 
quired by the eating of uncooked 
pork, since the ^- measles^' belonging to this parasite occur almost solely 
in the hog and in man. By means of its sucking -cups and its circlet 
of hooks it clings firmly to the mucosa of the intestine ; the remaining 
portions float freely in the intestine. Usually but a single parasite is 
present in the intestine, although the presence of several at the same 
time is not rare. Occasionally as many as thirty or forty have been ob- 
served in one individual. They excite irritation of the intestinal mu- 
cosa, colic, and reflex disturbances of the central nervous system. 

The measles" occur in the tissues of the hog, sometimes singly, 
sometimes in great numbers (Fig. 547), and individual organs, as the 
heart, for example, may be closely studded with them. 

In man, cysticerci occur in the most varied tissues — the muscles, brain, 
eyes, skin, etc. In the meninges and in the brain the measle may ap- 
pear in the form of mulberry or grape -like collection of cysts, known as 
cysticercus racemosus (Zenker). The cysts are for the greater part sterile, 
though some of them may contain a scolex. 

The importance of the measle depends upon its location, but is in gen- 




Fig. 547. — Cysticerci of the Tcenia solium, in the epi 
cardiura and myocardium of a hog. 



CESTODA. 



709 



eral slight. Its presence in the brain often causes se\'e]'e disturbances, 
but in other cases all signs of disease may be lacking. Locally it ex- 
cites a slight inflammation, which leads to a thickening of the connective 
tissue in its immediate neighborhood. The cyst may retain its vitality 
for years. After the death of the scolex the cyst contracts and there is 
deposited within it a chalky mass. The booklets are preserved in this 
mass for a very long time. Infection with the ''measles follows the in- 
troduction of eggs or proglottides into the stomach of man. 

Taenia mediocanellata or saginata sur- 
passes the Tcenia soUiim not only in length, 
as it measures 4-7 metres and more, but also 
in its breadth and thickness, as well as in 
the size of the proglottides (Fig. 548). 

The head is de\ oid of rostellum and circle 
of booklets (Fig. 549), has a flat crown and 
four large, powerful suckers, which are usu- 
ally surrounded by a black border of pig- 
ment. 

Tlie YY/^r/.y resemble tho^e of Tcenia solium. 
The fully de\eloped pregnant uterus (Fig. 
550) has a large uuni1)er of lateral branches 
^ which run close to each other, and instead 

g of branching dendi itically divide dichotom- 

U flT^ c^:M ously. The sexual opening lies back of the 

i W middle of the lateral border. The segments 
discharged spontaneously are for the greater 
part empty of eggs. 






Fig. Fig. 549. Fig. 550. 

Fig. 548.— Portions of a Tte/tta 8agi?iata. (After Leuckart.) Natural size. • 

Black pigmentation In and between the suckers. 



Fig. 549.- Head of Tamia saginata, retracted 
Unstained glycerin preparation. X 30. 

Fig. 5.50.— Segment of Toeuia saginat<i. (After Leuckart.) 



The measles" are found usually in the muscles and the heart, more 
rarely in the other organs of caWe (Cystieereus bovis). They are somewhat 
smaller than the measles found in pork. 



710 



THE ANIMAL PARASITES. 



The development follows a course similar to that of Tcenia solium. 
Malformations of this tapeworm are of very frequent occurrence. 

The parasite is acquired by man through the eating of raw beef. It 
has not been definitely settled whether the ''measles" of this worm occur 
in man, but some authors (Arndt, Heller) believe that such an occur- 
rence does take place. 

By means of its powerful suckers the parasite is able to cling very 
firmly to the intestinal wall. Stieda has observed a case in which a 
taenia 15 cm. long had penetrated through the wall of the duodenum into 
the pancreas, and had caused tissue -necrosis and haemorrhage in its 
neighborhood. 

Taenia cucumerina or elliptica is 15-20 cm. long, and possesses a head with ros- 
tellum and circle of hooklets. It is of very frequent occurrence in dogs and cats, but is 
rare in man. Its cysticercoid inhabits the louse and flea of the dog, more rarely the 
flea of human beings {Grassi). 

Taenia nana, a small tapeworm of from 8 to 15 mm. in length, has a head with 
four suckers and a circle of hooklets. It has been observed chiefly in Egypt and in 
Italy. B. Grassi was able to obtain several thousands of specimens from two Sicilians 
who had suffered from severe nervous disturbances. According to his investigations, 
the tspnia passes its entire development, from the embryo on, within the same host. 
Visamti (Rendiconti R. Istituto Lombardo, xviii., 1886) found, at the autopsy of a 
young man from northern Italy, great numbers of Tmnia nana in the lower portion of 
the ileum. In Germanv it has been observed in only a few cases {Mertens, I^icMenstern, 
Edder). 

Taenia diminuta (Mud.) ov flavopuucta (Weinland), minima {Grassi) is a tapeworm, 
20-60 mm. long, and has a head without hooklets. It is of common occurrence in rats 
and mice, and has also been observed in a few cases in man. According to Grof^si and 
Movelli, the measles live in a small butterfl3^ as well as in beetles. 

Von Linstow has recently described as Taenia africana a large tapeworm with 
scolex devoid of booklets, which he observed among the negroes of German East Africa. 

Besides those which also occur in man, tsenise are of frequent occurrence in the 
domestic animals, both in the carnivora and in birds, as well as in the herbivora. 

Tcenia marginata of the dog is a tapeworm, 1-5 m. long, provided with a double 
circle of hooklets. Its cysticercus forms cysts of varying size in and under the serous 
membranes of sheep, cattle, goats, and hogs. 

Tcenia serrata is a taenia found in the dog. It is 50-100 cm. long, and possesses a 
circle of hooklets. The cysticerci are found in rabbits and hares. 

TcEnia ccEnurus is a tapeworm of the dog, 40-100 cm. long, and is provided with 
hooklets. It passes its cystic stage most frequently in sheep, where it seeks the central 
nervous system and forms cysts varying in size from that of a millet seed to that of a 
hen's egg, which contain great numbers of scolices. Its presence in the brain gives rise 
to the so-called " staggers " of sheep. 

Tcenia pUcata (10-25 cm. long), Tcenia mamillana (1-3 cm. long), and Tcenia perfo- 
liata (3-5 cm. long) occur in horses. Tcenia expansa (4-5 m. long) and Tcenia denticu- 
lata (25-80 cm. long) are the common tapeworms of cattle. Further, still other formi 
of taeni* occur more rarely as parasites in sheep and cattle. 



Literature. 

{Tcenia as Intestmal Parasites. ) 

Blan chard: Gestodes monstrueux, Paris, 1894, ref. Cbl. f. Bakt., xvii., 1895. 
Blochmann : Plasmatische Langsgefasse bei Taenia sas:. u. Taenia sol. Cbl. f. Bakt., 
xii., 1892. 

Braun: Die embryonale Entwickelung der Ccstoden. Cbl. f, Bakt., 1889; Helmin- 

tholog. Notizen. lb., xiv., 1893. " 
Erlanger: Der Geschlechtsapparat v. Taenia echiuococcus. Zeitschr. f. wiss. Zool., 

50 Bd., 1890. 

Grassi, B., u. Rovelli, G. : Embryolog. Forschungen an Cestoden. Cbl. f. Bakt., v., 
1889. 

Guillebeau: Helminthologische Beitrage. Virch. Arch., 119 Bd., 1890. 
Huber : Bibliographic d. klin. Helminthologie, 1-4 Hefte, Mtinchen, 1891-92. 



CESTODA. 



711 



Joseph.: Das centrale Nervensystem d. BandAviirnier. Tagebl. d. Naturforscheivere, 
Berlin, 1886. 

Kahane: Anatomie von Taenia perfoliata. Zeitschr. f. wiss. Zool, xxxiv. 
Kitt: Lebrb. d. pathol. -anat. Diagnostik, ii., Stuttgart, 1895. 

Leichtenstern : Taenia nana ii. flavopunctata beim Menschen. Deut. med. Woch., 
1892. 

V. Liinstow: Taenia nana u. murina. Jen. Zeitschr. f. Natiirwiss., 1896. 
liutz: Beobacht. lib. Taenia nana u. flavopunctata. Cbl. f. Bakt., xvi., 1894. 
Ming-azzini : Sur le mode d'adbesion des cestoides a la paroi intestinale. Arch. ital. 
de biol., xxxii., 1899. 

Niemie: Ueb. d. Nervensystem d. C'estodeu. Arb. a. d. Zool. Inst. d. Univ. Wien, 
xii.. 1886. 

UTuttall: The Poisons Given Off bv Parasitic Worms in Man and Animals. Amer. 

Nat., 1899. ■ • 

Peiper: Thier. Parasiten d. Men.schen. Ergebn. d. allg. Path., iii., 1897 (Lit.). 
Roder: Taenia nana in Deutschland. Mimch. med. Woch., 1899. 

Sommer: Ueber Bau u. Entwickelung der Geschlechtsorgaue v. Taenia mediocanellata 

u. Taenia solium, Leipzig, 1874. 
Stieda: Durchbobrung d. Duodenums u. d. Pankreas durch. e. Taniae. Cbl. f. Bakt., 

xxviii. 1900. 

Stiles: The Tvpe Species of the Cestode Genus Hymenoleins. Bull. U. S. Hyg. Lab., 
No. 13, May, 1903. 

Stiles and Hassall: A Revision of the Adult Cestodes of Cattle, Sheep, and Allied Ani- 
mals, Washington, 1884; Tapeworms of Poultry, Washington, 1896. The Inspec- 
tion of Meats for Animal Parasites, U. S. Dept. Agr. Bull., 19, 1898. 

Ward: A New Human Tapeworm {Tcp/rda confusa). West. Med. Rev., 1896; Zool. 
Auz., 1897; Cestoda. Ref. Hdb. of Med. Sc., 2d ed., vol. ii. 

Weinland: Human Cestodes, Cambridge, 1858. 

Zschokke: Studien ilber den anatom. u. bistol. Bau der Cestode. Cbl. f. Bakt., i., 
1887; Rech. sur la structure des Cestodes, Bale, 1889. 



( Cysficercus in Man. ) 

Askanazy: Cysticerkenbildung an der Hirnbasis. Beitr. v. Ziegler, vii., 1890. 
Bitot et Sabrazes: Etude sur les C3^sticerquesen grappe de I'encephaleet de la moelle 

(•he/ riiomme. Gaz. med. de Paris, 1890. 
Dolina: Intraocularer Cysticercus. Beitr. v. Ziegler, v., 1889. 
Hirschberg": Cysticercus im Auge. Eulenburg's Realencyklop., 1885. 
V. Kahlden: C'Vsticercus d. lY. Ventrikels. Beitr. v. Ziegler, xxi., 1897. 
Kratter n. Bohmig": Freier Geliirncysticercus. Beitr. v. Ziegler, xxi., 1897. 
Lewin: Cysticercus celluloste der Haut. Eulenburg's Realencyklop., 1885 (Lit.); 

Arch. f. Derm., 26 Bd., 1894 (Lit.). 
Mennicke: Cysticercus racemosus d. Gehirns. Beitr. v. Ziegler, xxi., 1897. 
Richter: Cysticercus racemosus in den inneren Meningen. Prag. med. Woch., 1891. 
Zenker: Ueber den Cysticercus racemosus des Gehirns. Bonn, 1882. 

§ 185. The Taenia echinococcus lives in the intestinal canal of the 
dog. It is 4-5 mm. long and possesses only four segments, the most 
posterior of these surpassing in length all the rest put together (Fig. 
551). 

The small hooklets have coarse root processes and are implanted upon 
a rather bula^ing rostellum. Their number runs from about thirty to 
fifty. 

The cyst=worm (hydatid) alone is found in man. It results from 
the introduction of ttenia eggs into the intestinal canal. 

If the embryo wanders from the intestinal canal into any organ, it 
changes into a cyst, which is not capable of active motion. It consists of 
an outer lamellated, very elastic cuticle (Fig. 552, a) and a parenchyma- 
tous layer (b) lying internal to this, consisting of granular masses and 
cells, and containing muscle-fibres and a vascular system. When the 
cyst has reached about the size of a walnut (sometimes earlier), there are 
formed from the parenchymatous layer small brood- capsules (c) which 



7l2 



THE ANIMAL PARASITES. 



pi oduce a great number (vH ,scolices. The lirst sla<;(' of these tai^eworm 
heads consists of coarsely granular pi otoi)lasiiiic masses (d) lying in the 
wall of the brood-capsule; these develop further and show 
cavities (e) communicating with the cavity of the brood- 
capsule, and later become differentiated into a tapeworm head 
(/) furnished with a circle of hooklets. The head (h) which 
now protrudes into the lumen of the brood-capsule (g, h) is 
about 0.3 mm. long, X30ssesses a rostellum with small, plump 
hooklets, four suckers, a water -vascular system, and numerous 
chalky bodies in its i^arenchyma. Frequently the anterior 
part of the body is telescoped into the posterior i3art (g). 

In many cases the echinococcus cyst remains single. 
Its only change consists in an enlargement to the size of an 
orange or fist, through the formation of new brood-capsules 
and heads. The surrounding tissue forms a connective-tissue 
capsule, in which the cuticular cyst lies. The cavity of the 
cyst is filled with a clear fluid, which does not coagulate 
through boiling or on the addition of acids, and contains none 
or but little albumen, but on the other hand does contain 
sodium chloride, calcium oxalate, triple phosphates, uric acid, 
sugar (in the liver), and often also cholesterin. The brood- 
capsides are always situated on the inner surface, in case they 
are not mechanically dislodged ; and are visible through the 
transparent parenchyma as small white points. Occasionally 
the cyst remains sterile. 
In many cases daughter=cysts (Fig. 553, 6') are formed. Their de- 
velopment proceeds in the depth of the cuticle independently of the real 
parenchymatous layer. Between two lamellae of the cuticle there arises 



Fig. 551.- 
FU'll -grown 
Tsenia echino- 
coccus. (Af- 
ter Leuckart.) 
X 13. 




Fig. .552.— Wall of an echinocoeciis-cyst containing brood-capsules and scolices (alcohol, carmine), a, 
Chitinous membrane; b, parenchymatous layer with vesicular cells; c, brood-capsules; t/, e, /, g, h, 
scolices in different stages of development. X 100. 

a collection of granules, which surround themselves with a cuticle, and 
thereby become the centre of a new set of layers. As the number of 
layers increases, the cavity grows larger and the contents beconie cleai-. 



ECHINOCOCCUS. 



713 



If the daughter-cysts grow they bulge out the wall of the mother-cyst 
like a hernial sac, until it finally gives way and liberates its contents. 
If they now pass outward by the side of the parent-cyst, they obtain from 




Fig. 55d.—EcMnococcus hydatidosus. a. Surface of liver; b, indurated connective tissue; c, 
daughter-cysts vpithin a parent-cyst, which has been opened by an incision; d, adhesions. Three-flfths 
natural size. 

the parenchyma in which they lie an external capsule of connective tis- 
sue, and then produce brood capsules in the same manner as the primary 
cysts arising from the six-hooked embryos. 

An echinococcus with an exogenous proliferation is called echinococcus 
granulosus (scolecipariens Kiichenmeister), or sometimes also echinococ= 
cus veterinorum from the fact that it is of frequent occurrence annmg 
the domestic animals. 

A second compound form of the echinococcus is the echinococcus 
hydatidosus. It is characterized by the presence of inner daughter -cysts 
(Fig. 553, c). According to statements made by Naunyn, and also con- 
firmed by Leuckart, the scolices and brood -capsules undergo a cystic 
metamorphosis, and so become changed into daughter-cysts which occa- 
sionally produce grand -daughter cysts. Through the formation of numer- 
ous daughter-cysts the chief cj^st may attain a very large size. 

The infection of man follows the ingestion of the eggs of the taenia 
which occurs in dogs. The cysts are most often found in the liver, 
btit the echinococcus occasionally occurs in the most diverse organs — for 
example, in the lungs, spleen, kidneys, intestine, in a bone or in the 
heart. With the exception of the disturbance of the tissues from press- 
ure and of the local inflammation which it causes (the latter leading to 
the formation of a connective-tissue capsule in many organs) the cyst often 



Y14 



THE ANIMAL PARASITES. 



produces no harmful effects upon the affected individual. It often dies 
on attaining a certain size (that of a walnut to that of an apple), the 
fluid is absorbed, the cyst contracts, and there remains within it a fatty, 
cheesy detritus, which often calcifies to a mortar-like mass. The hook- 
lets are preserved for a very long time. 

In other cases the echinococcus becomes larger, particularly when 
endogenous or exogenous daughter -cysts develop. It may become dan- 
gerous through its size alone. Severe inflammations are occasionally 
produced, particularly after trauma or after rupture of the cyst into one 
of the body-cavities. Enpture into a blood-vessel may also occur and 
lead to the metastasis of cysts and an embolic blocking of vessels. In more 
favorable cases rupture may take place externally or into the intestines. 

The spontaneous spread of brood -capsules and scolices in the same 




Fig. 554.— Transverse section of an Echinococcm mult Hoc ulari^. o, Alveolar echinococcus tissue; ft, 
liver tissue ; c, cavity produced by softening ; d, fresh nodules. Natural size. 

host, as well as the experimental transplantation of the same into another 
host (Alexinsky) may lead to the formation of new cysts. 

The form of the i:)arasite known as echinococcus alveolaris or 
multilocularis presents itself as a hard tumor, situated usually in the 
liver, rarely in other organs (brain, spleen, adrenal), and possesses an 
alveolar structure (Fig. 554), in that a firm, dense connective -tissue mass 
encloses numerous cavities. Its contents are translucent and gelatinous, 
or consist of fluid and a gelatinous substance. The cavities are in part 
si)he]ical and in part irregular in shape. Usually, through the soft- 
ening and disintegration of the parenchyma, ulcerative cavities (c) are 
formed. In other places the tissue is fibrocaseous, necrotic or calcified, or. 
is impregnated with bile. At times the caseation of the proliferating tis- 
sue is the most prominent feature of the process ; at other times the alve- 
olar structure. When the development of the colonies has progressed 
further, there appear in the tissue gray and yellowish nodules (d) in which 
cavities containing colloid plugs (chitin-cysts and coils) are de^'eloped. 



ECHINOCOCCUS. 



715 



The exquisite a^lveolar structure lias given rise to the theory that this 
form of echiuococcus is au alveolar, colloid- containiug tumor of the liver. 
Virchow first recognized the true nature of the condition, and demon- 
strated that the so-called colloid masses were echiuococcus cysts. 

According to the investigations of Melnikow-Easwedenkow the alve- 
olar echiuococcus is to be regarded as a different species, which increases 
in the tissue of the host in a peculiar manner, suggesting the mode of 
development of the Trematodes; and in many cases spreads by both 
haematogenous and lym])hogenous metastases from the primary focus of 
development to other organs (lymph-glands, lungs, brain). 

The embryo migrating from the intestine into the liver becomes 
changed into a multilocular chitinous coil, which possesses on both inner 
and outer sides granular masses of protoplasm, from which in part sco- 
nces^ and in part ovoid embryos develop. These, through virtue of their 
motility, become distributed in the tissues and give rise to proliferations 
of granulation tissue with the formation of epithelioid cells and multinu- 
clear giant-cells, terminating partly in tissue-indurations and partly in 
caseation. The latter process is particularly prominent in metastatic 
foci. Among the structures which arise from the granular protoplasm 
of the parasite there maybe distinguished the following forms: (1) 
ovoid embryos with thin homogeneous membrane ; (2) embryos with thick 
fibrous capsules ; (3) scolices. 

The embryos which are capable of migration are to be found inside of 
the chitin-cysts as well as free between the tissue-cells. A part of the 
embryos wandering thence into the connective tissue of the organ develop 
within the vessels into complicated chitin-cysts or coils which again form 
an af ter-growlh of embryos ; another part die and are taken up by phago- 
cytes or are infiltrated and disintegrated. 

Scolices form from the granular protoplasm of the embrj^o (prosco- 
lices) inside of the chitin- structure as well as outside of the same. The 
proscolices entering the tissues may also be changed into chitin-cysts. 

The life-history of the alveolar echiuococcus outside of the paren- 
chyma of the organ is unknown ; the feeding to dogs has given no posi- 
tive results. It appears that the embryos and scolices of the same are not 
capable of development in the intestine of the dog. 

The ordinary echiuococcus is widely distributed, though not very 
common. It is of most frequent occurrence in Iceland, where the inhabi- 
tants live in very close association with dogs. The alveolar echiuococcus 
has beeu observed chiefly in Switzerland, South Germany, Austria, and 
in Eussia. 

Literature. 

(JEchinococcus. ) 

Abee: Ueber multilociilaren Echinococcus. Virch. Arch., 157 Bd., 1899. 
Alexinsky: Verimpfiing von Echinococcus in d. Banchhohle. Langenbeck's Arch., 
56 Bd., 1898. 

Bider: Echinoc. multilocul. des Gchirns. Virch. Arch., 141 Bd., 1895. 
Carriere: De la tumeur hydatique alveolaire, Paris, 1868. 

Doebbelin: Knochenechinokokken d. Beckens. Deut. Zeitschr. f. Chir.,48Bd., 1898. 
■Erlanger: Der Geschlechtsapparat d. Taenia echinococcus. Zeitschr. f. wiss. Zool., 
50 Bd., 1890. 

Gerulanos: Multiple Muskelechinokokken. Deut. Zeitschr. f. Chir., 48 Bd., 1898 
(Lit). 

Guillebeau: Histologie des multilocularen Echinococcus. Yirch. Arch., 119 Bd., 1890. 
^ouzel: Cystes hydatiques du rein. Rev. de chir., 1898. 



716 



THE ANIMAL PARASITES. 



Huber: Bibliographie d. klin. Helminthologie, i., Miinchen, 1891. 

Klemm: Futterungsversuche m. Ech. multilocul. Bayr.- arztl. Correspbl., 1883. 

Madelung' : Beitr. z. Lehre von den Echinokokken, Stuttgart, 1885. 

Mangold: Ueb. d. inultiloc. Echinococcus. Berl. klin. Woch., 1882. 

Melnikow-Raswedenkow : Stud, liber den Alveolarechinococcus. Beitr. v. Ziegler. 

iv., Supplli., Jeua, 1901. 
Mosler: Ueber Milzechinococcus, Wiesbaden, 1884. 

Miiller: Zur Kenntn. d. Taenia echinococcus. Mimch. med. Woch., 1893. 
Naunyn: Eutwickelung d. Echinococcus. Dorpat. med. Zeitschr., 1870. 
Neisser, A. : Die Echinokokkenkrankheit, Berlin, 1873. 

Ostertag": Ueb. d. Ech. multil. bei Rindern u. Schweinen. Deut. Zeitschr. f. Thier- 
med., xvii., 1890. 

Posselt: Die geographische Verbreitung des Blasenwurmleidens, Stuttgart, 1900 (Lit.). 

Riemann: Keimzerstreuung d. Echinococcus. Beitr. 

V. Bruns, xxiv., 1899. 
Sommers : Statistics on Echinococcus Disease in the 

United States. N. Y. Med. Journ., 1896. 
Tscliniarke: Beitr. z. Histologic des Echinococcus 

multilocularis. Inaug.-Diss., Freiburg, 1891. 
Vierordt: Abhandlung iiber den multilocularen Echi- 
nococcus, Freiburg i. B., 188(5. 
Virchow: Yerh. d. ph3^s. med. Ges., vi., Wurzburg, 

1855; Yirch. Arch., 6 Bd., 1854. 
Wilms: Echinoc. multiloc. d. Wirbelsaule. Beitr. v. 
Bruns, xxi., 1898 (Lit.). 

§ 186. Bothriocephalus latus (Breniser) 
or pithead is the most formidable tapeworm 
of man, measuring from 5-8 metres in length, 
and consisting of three thousand to four 
thousand short but broad segments (Fig. 
555), which are broadest in the middle region 
and narrower again at the end. The length 
of the largest segment is about 3. 5 mm. , the 
breadth about 10-12 mm. 

The head (Fig. 556) has a long oval or 
club shape, is about 2.5 mm. long and 1 mm. 
broad. It is somewhat flattened, and pos- 
sesses on each lateral margin a slit-like de- 
pression, and is mounted upon a filiform neck. 

The body is narrow and flat 
like a ribbon, with the exception 
of the central parts of the seg- 
ments which project somewhat 
outward. At this spot the uter- 
us is found, in the shape of a 
single canal, which forms a 
number of coils (Fig. 557, m). 
When the eggs collect here in 
great numbers the lateral coils 
of the uterus arrange themselves 
in folds, so that a remarkable 
rosette-like appearance is pro- 
duced. The sexual oiDcnings lie 
in the middle line of the ventral 
surface, near to the anterior 
border of the segment, the fe- 
male orifice (o) being close behind the male opening (/). 

The ovary {g) is a double organ which lies in the middle layer; the 




laius. 




Fig. 555. 

Fig. 5o5.—Bi)thri<>cephahi^. 
art.) Natural size. 

Fig. .5.56. — Head of Bnthrincephalm latus of 
Bremser. (After Heller.) Enlarged. 



BOTHRIOCEPHALUS LATUS. 



yolk -chambers (/«), on the other hand, are located iu the cortical layer. 
The shell-gland (Jc) lies behind the collecting-tube {i) of the yolk-cham- 



\ \ 




Fig. 557.— Median portion of a proglottis of Bothriocephalus lotus, seen from the dorsal surface. The 
cortical layer of the segment has been removed except a border on each side, and the middle layer thus ex- 
posed. (After Sommer.) a. Lateral vessels ; h, testicular vesicles ; c, testicular canaliculi ; d, seminal ducts ; 
e, posterior, /, anterior hollow-muscle apparatus (cirrus-sac of vas defei'ens) ; g, ovary ; 7i, yolk-chambers 
lying :n the cortical area; -i, collecting-duct of yolk-stalk, branches of vrhich lead ventrally to the yolk- 
chambers ; k, shell-gland ; Z, beginning of the uterus ; m, loop of uterus filled with eggs, the orifice of 
uterus opening on the anterior surface; n, vagina; o, vaginal opening. X 35. 



bers. The testicles consist of clear vesicles Q)) which lie in the lateral 
portions of the middle layer, and communicate by means of fine canals 
(c) with the vas deferens {d), which terminates in the cirrus-sac (<?,/). 

The eggs (Fig. 558) are oval, and are about 0.07 mm. long and 0.045 
mm. broad. They are surrounded by a thin, brown shell, the anterior 
pole of which forms a sharply outlined 
cap-like cover. ,-'^f,TfT 

The Bothriocephalus lotus occurs chiefly 
in Switzerland, in the northeastern parts 
of Europe, in Holland and in Japan, and 
lives, as does the Tsenia, in the intestine 
of man. According to Bollinger it is 
rather frequent in 



Munich. The first 
stage of development 
of the eggs takes place 
in water. After the 
lapse of months there 
develops an embryo 
( Oncosphmra) armed 
with six booklets and 
covered with cilise 
(Fig. 559). This de- 




Fig. 558. 



FIG. 559. 



Fig. 558.— Eggs of Bothriocephalus latus, the one at the right 
having been emptied of its yolk-contents. (After Leuckart.) 

Fig. 559.— Free embryo of Bothriocephalus latus with ciliated en- 
velope. (After Leuckart,) 



718 



THE ANIMAL PARASITOS. 



velops, in some intermediate host as yet unknown, into a measle {Flero- 
eercoid), which, according to the investigations of Braun in the Russian 
Baltic provinces, seeks out as second intermediate host the pike or tad- 
pole, and develops in the muscle or internal organs of these animals into 
a sexless tapeworm. According to Grassi and Parona, the measle of 
Bothriocephalus latus in Italy occurs in the x)ike and in the river-iDerch. 
In Japan it is found most frequently in the OnehoyJiijnclms Ferryi (Tjima, 
Leuckart). Zschokke found it in the Lake of Geneva in the following 
forms of fish: Lota vulgaris, Ferca fluviatiJis, Sah)W umhJa, Esox hicius, 
Trutta vulgaris, and Trutta lacustris. It is found most often in the tadpole 
{Lota vulgaris) and in the perch (Ferca fluviat His) . Should the measle gain 
entrance, through the ingestion of the fish mentioned, into the intestinal 
canal of man, it again attains sexual maturity. According to Braun and 
Parona the measles may also be brought to development in both dogs and 
cats. The presence of Bothriocephalus in the intestine gives rise to a 
gradually increasing anaemia, which resembles pernicious ansemia. The 
diminution of the red blood-cells and of the hsemogiobin content of the 
blood is probably due to the fact that after the death of the tapeworm 
poisonous products arise having an injurious action upon the blood-cor- 
puscles. 

Bothriocephalus cordatus (Leuckart) is a tapeworm, of 80-115 cm. long, and lias 
a heart-shaped head, whose sucking-grooves are flattened. The breadth of the ripe 
segments is about 7-8 mm. ; the length, about 3-4 mm. In Greenland and Iceland it is 
a frequent parasite of the dog, seal, and w^alrus, and is found occasionally in man. The 
measles likewise occur in fishes. 

Bothriocephalus Mansoni (Cobbold) or liguloides (Leuckart) is the measle (plerocercoid) 
of a tapeworm which has been observed a few times (Manson, Ijima, Murata) in the 
body-tissues and in the descending urinary passages or in the urine. Its origin is not 
known. 

Literature. 

(Bothriocephalus Latus. ) 

Bollinger: Bothrioceph. latus in Mlincheu. Deut. Arch. f. klin. Med., xxxvi., 1885. 

Braun: Virch. Arch., 88 u. 92 Bd. ; Zur Entwickelungsgeschichte des breiten Band- 
wurmes, Wurzburg, 1885; Ueber den Zwischenwirth des breiten Bandwurmes, 
Wiirzburg, 1886; I)ie thier. Parasiten des Menschen. Wurzburg, 1895. 

Grassi, B., e Rovilli: Contrib. alia studio dello sviluppo del Botriocefalo lato. Giorn. 
delJa R. Accad. di Med., 1887, ref. Cbl. f. Bakt., iii., 1888. 

Leuckart: L. c, und Zur Bothriocephalus-Frage. Cbl. f. Bakt. u. Parasitenk., i., 1887. 

Parono: Rendiconti 1st. Lomb., vol. xix. 

Schaumann: Zur Kenntniss der Bothriocephalus-Anamie, Berlin, 1894. 

Scliaumann u. Tallqvist: Blutkorperchen auflosende Eigensch. d. breiten Baud- 

w^urmes. Deut. med. Woch., 1898. 
Sommer: Ueb. d. Bau d. geschlechtsreifen Glieder v. B. latus, Leipzig, 1872. 
Vanlair : Gas de Bothriocephalie en Belgique. Bull, de I'Ac. Rov, de Belgique, xviii., 

1889. 

Wilson: Bothriocephalus latus (United States). Amer. Journ. of Med. Sc., 1902 
(Lit.). 

Zschokke: Bothrioceph. latus in Ganf. Cbl. f. Bakt., i., 1887; Zwisclienwirth d. 
Bothr. latus. lb., iv., 1888. 

B. I^^EMATHELMINTHES (EOUND WORMS). 

§ 187. All the round worms which occur as parasites belong to the 
Nematoda. They possess a slender, cylindrical, elongated, at times 
filiform body without segments or appendages. The cuticle is thick and 
elastic. The mouth opening is found at one extremity, and js provided 



ASCARIS LUMBRICOIDES. 



719 



sometimes with soft and sometimes 
with horu-like lips. The elongated in- 
testine, together with the pharynx and 
chyle-stomach, extends through the en- 
tire body -cavity (Fig. 560) and opens 
upon the ventral surface a short dis- 
tance from the (usually) awl-shaped 
posterior extremity. The sexual or- 
gans and their openings are also found 
on the ventral surface. The female 
sexual orifice is located at about the 
middle of the body, less frequently 
near the anterior or posterior extremity 
(Fig. 560, A, a). In the male the sex- 
ual opening and the anus are located 
together (B, c). The chitinous cover- 
ing of the lower gut forms in the male 
the means of clinging during the act 
of copulation. The males are usually 
smaller than the females. The de- 
velopment is direct, and the metamor- 
phoses are not striking. The nema- 
todes occurring in man are in part 
harmless parasites of the intestine, and 
in part very dangerous, sometimes even 
fatal, parasites of various organs. 

§ 188. Ascaris iumbricoides, the 
common round- worm (Fig. 560) is a 
light-brown or reddish, cylindrical 
worm with tapering ends. The female 
(^) is 25-40 cm. long, the male (B) is 
much smaller, and the posterior ex- 
tremity of the latter is bent in the 
form of a hook and provided with two 
spicules (c) or chitin processes. 

The mouth opening (5) is sur- 
rounded by three muscular lips bearing 
fine teeth. The female sexual opening 
(A, a) lies anterior to the middle of 
the body. The eggs which the mature 
female contains in enormous numbers 
possess in their fully de\^eloped con- 
dition a double shell (Fig. 561) and 
around this an albuminous envelope. 
They are about 50-70 /j. in length. The 
worm inhabits the entire intestinal 
tract, but most frequently the small in- 
testine. It is the most common par- 
asite of man, and is found frequently 
in very great numbers. When mature 
females are present the faeces contain 
the eggs in great numbers. These are 
very resistant to external influences, 
for example, to drying and freezing. 




(After Perls.) Female; B, male. 

Natural size. At a is the female sex- 
ual orifice ; c, tbe two spicules of the male ; b, 
the (enlarged) cephalic end with the three lips. 



Fig. 561.— Egg of Ascaris Iumbricoides, 
with shell and albuminous covering. (After 
Leuckart.) X 300. 



720 



THE ANIMAL PARASITES. 



The eggs require no interniediate host (Lutz, Leuckart, Grassi, Ep- 
stein). Man is infected by the ingestion of eggs which have been 
expelled from the bowel and haA^e matured in the faeces. According to 
feeding-experiments which Epstein carried out on human beings with 
eggs which had been cultivated in damp faeces for a long time, the round- 
worm attains its maturity in from ten to twelve weeks after the ingestion 
of the eggs. At this time the male is 13-15 cm. long, and the female 
from 20-30 cm. Their presence in the intestine does not cause any no- 
ticeable disturbance. Only when iDresent in large numbers do they some- 
times, especially in children, cause intestinal catarrh, vomiting, nervous 
disturbances and convulsions. Occasionally the worm crawls into normal 
and pathological openings in the wall of the intestinal canal, and in this 
way causes trouble. Thus, when it crawls into the ductus choledochus, 
it may produce bile-stasis. If it penetrates through an ulcer into the 
peritoneal cavity or into a hernial sac, it may excite inflammation of 
the tissues concerned. According to Leuckart it may also penetrate the 
uninjured intestinal wall. It is very frequently i3assed with the stools 
per anum, but at times per os in vomiting. From the pharynx it may 
wander into the larynx. 

In the domestic animals ascarides are of frequent occurrence. Ascaris lumbri- 
coides is found in swine {Ascaris suilla) and in cattle {Ascaris mtuli). Ascaris megalo- 
cepJiala, a round worm whose female is 18-37 cm. long, is a common parasite of the 
horse and donkey. Ascaris mystax, whose female reaches a length of 12 cm., is found 
frequently in dogs and cats, and has also been observed in man. Various species, des- 
ignated as Heierakis, occur in birds. Heterakis maculosa, the round worm of pigeons, 
may cause the death of the pigeon when occurring in large numbers within its intestine. 



Literature. 

{Ascaris Lumbricoides.) 

Epstein: Uebertragung des Spulwurms. Jahrb. f. Kinderheilk., 33 Bd., 1892. 
Grassi: Intorno all' Ascaris lumbricoides. Gazz. degli Ospetali, ii., 1881, u. Cbl. f, 

Bakt., iii., 1888; Trichocephalus- und Ascarisentwickelung. Ibid., i., 1887. 
Huber: Bibliographic der klin. Helminthologie, Miinchen, 1893. 
Kitt: Lehrb. d. path.-anat. Diagnostik, ii., Stuttgart, 1895. 
Leuckart : Uebergangsweise des Ascaris lumbricoides. Cbl. f . Bakt. , 11. , 1887. 
liutz : Zur Frage der Invasion von Taenia elliptica u. Ascaris lumbricoides. Cbl. f . 

Bakt., ii., 1887; Uebertragung des menschlichen Spulwurms. lb., iii., 1888. 
Peiper: Thierische Parasiten. Ergebn. d. allg. Path., iii., 1897. 
Saltykow: Ascaridosis hepatis. Zeitschr. f. Heilk., xxi., 1900. 

§ 189. Oxyuris vermicularis, awl-tail, pinworm, or threadworm is a 
small roundworm (Fig. 562), the female being about 10 mm. long (a, b) 
and pointed at the caudal extremity like an awl, while the male is about 
4 mm. long (c) with a blunt posterior end, the anus being provided with 
a spiculum. 

The eggs (563, a), which the body of the female often contains in 
very great numbers, are 50 /j. long and 24 p. broad, have a flat and a 
curved surface, and a shell which is covered by a thin albuminous layer. 
Oxyuris vermicularis inhabits the large intestine and the lower portion of 
the small intestine. According to Zenker and Heller only the impreg- 
nated mature females are found in the large intestine, the young individ- 
uals and the males remain in the small intestine. They occur very fre- 
quently in larger or smaller numbers. At night they often wander from 
the rectum over the anal region, and may enter the vagina ; they excite 



ANCHYLOSTOMA DUODENALE. 



721 



itching of the affected parts. The scratch- 
ing thus produced sometimes leads to der- 
matitis, erections, masturbation, etc. 

For the development of the eggs (Fig. 
563 a-e), it is necessary after their expul- 
sion with the faeces that they again be 
taken into the stomach of man or beast. 
It is very probable that the original host 
may again infect himself with oxyuris, in 
that, for example, the eggs becoming at- 
taclied to his finger during the act of 
scratching may later get into his mouth. 

The eggs are very resistant to drying, 
and in this condition may be widely scat- 
tered. 

§ 190. Anchylostoma duodenale 

{Dochmius duodenalis, or Strongylusduodena- 
Us, or Uncinaria duodenalis, also Uncinaria 
Americana [StilesJ), Hook-worm, is a small 
worm belonging to the family of Stron- 
gylides, which inhabits the upper part of the 
small intestine (Fig. 564). The cylindrical 
body of the female is 5-18 mm. long, that 
of the male 6-10 mm. The cephalic end 
(Fig. 565) is curved toward the dorsal sur- 
face, and possesses a bellied mouth-capsule 
(d). It is almost completely divided dor- 
sally, and the cleft is covered by two chitin- 
ous layers. On the ventral border there 
are four incurving teeth (&), on the dorsal 
border two teeth which are perpendicular- 
ly placed (c), all being held together by 
chitinous bands. 

The male is provided at its caudal extremity with a threefold bursa 
(Fig. 564, i), and two thin, fishbone-like spicules (p). In the female 
the posterior end is pointed, and bears an awl-shaped spine ; the vulva 

lies posterior to the body centre. The oval 
eggs (Fig. 566) are 44-67 ^ long, 23-40 fx 
broad. They undergo the first stages of cleav- 
age in the human intestine (a-d), develop 
further in muddy water (e, f ), and may then, 
if brought into the human intestinal tract, de- 
velop again into se xually mature animals. With 
its teeth the worm works its way into the 
mucous membrane as far as the submucosa, and 
sucks itself full of blood. Its point of attack 
is distinguishable later by a small ecchymosis 
in the middle of which there is a white spot 
with a central perforation. Occasionally there 
are found in the intestinal mucosa small cav- 
ities filled with blood, within each of which 
there lies a coiled-up worm. The parasites, 
when present in large numbers, cause a con- 
tinuous and serious loss of blood, which may 




Fig. 563. — Oxyuris vcrmicularis. 
a. Sexually mature female; h, female 
full of eggs; c, male. (After Heller.) 
X 10. 




Fig. 563. 



Eggs of Oxyuris 
vermicularis in different stages 
of development. (After Zenker 
and Heller.) a, b, c. Segmenta- 
tion of yolk; d, tadpole-shaped 
embryo ; t\ worm-shaped embryo. 



X 21 



38 



T22 



THE ANIMAL PARASITES. 



lead to the most severe forms of anaemia (^Egyptian chlorosis), but they 
are not infrequently found in individuals who j^resent no symptomis of 




Fig. 564. 

Fig. 564. — Mivle of Anchylostoma duodendle. (After Schulthess.) a, Head with mouth-capsule ; 
b, oesophagus ; c, intestine ; d, anal-glands ; e, cervical glands ; /, skin ; g, muscle-layer ; ?i, porus ex- 
cretorius ; i, triple bursa ; 7c, ribs of the bursa ; Z, testicular canal ; m, seminal vesicle ; w, ejaculatory 
duct ; o, groove of latter ; penis ; g, penis sheath. X 18. 

Fig. 565.— Cephalic end of Anchiilostoma duodenale. (After Schulthess.) a. Mouth-capsule ; 5, te(>tli 
of ventral border ; c, teeth of dorsal border ; d, mouth cavity ; e, skin protuberance on ventral side of 
head ; /, muscular layer ; dorsal groove ; Ji, oesophagus. 

Fig. 566.— Eggs of Anchylostoma duodenale. (After Perroncito and Schulthess.) a-d, Different 
stages of segmentation ; e, /, eggs with embryos. X 200. 



disease. The parasite is very common in the tropics, and also in Japan. 
According to. Griesinger and Bilharz about one -quarter of the native 



STRONG YLIDES. 



723 



EgyptiaDS suffer from this disease. The parasite was very often ob- 
served in the workmen engaged in the Saint Gotthard tunnel. Accord- 
ing to Menche and Leichtenstern the brick-fields of the Ehine provinces 
are to a great extent infected with anchylostoma (brick -burner's anae- 
mia). (For the distribution of TJncinaria Americana, see Stiles, Bull. U. 
S. Dept. of Agric, 1902.) 

Eustrongylus gigas, a palisade-worm of red color, whose female reaches a length 
of 1 metre, is a very rare parasite, which has been observed only a few times in the kid- 
ney-pelvis of man. It occurs very frequently in dogs. It possesses a mouth-opening 
with six papillse ; the male has on its posterior extremity a bursa with a single spicu- 
lum. The eggs are oval, 0.06 mm. long, and provided with a rough albuminous 
capsule. 

Strongylus longevaginatus, a thread-like, white worm, 26 mm. long, was once 
observed in the lung of a boy. 

In the domestic animals Strongylides occur in much greater numbers than in man, 
and are in part inhabitants of the intestine, and in part of the lungs {Midler, "Die 
Nematoden der Saugethierlungen," Z)ew^. Zeiischr. f. Thiermed., xv., 1886). 

DocJimius trigonoceplialus and Dochmius stenocephahis occur in the intestine of dogs, 
and give rise to anaemia. 

Strongylus armatus is a common parasite of the horse, which enters the intestinal 
tract as an embryo, bores into the intestinal wall {OU), thence into the liver, by way of 
the portal vein, and further into the lungs and the organs of the major circulation. 
Following this migration, it ma}^ develop in the most diverse organs and cause the 
formation of fibrous nodules, which become calcified after the death of the parasite 
enclosed in them. In the intestinal wall it may develop after direct migration or after 
embolic lodgment in the part, and leads to the formation of cavities, from which it 
again breaks through into the intestinal lumen. In the mesenteric arteries it attains 
sexual maturity, and causes thrombosis and the formation of aneurisms. The male of 
the mature worm is 20-30 mm. long; the female, 20-55 mm. 

Strongylus tetracanthus, which inhabits the large intestine of the horse, causes a 
haemorrhagic enteritis when present in large numbers. 

Strongylus paradoxus is an extremely common parasite of the lungs of hogs. 
Strongylus capillaris, Sir. commatatus, and Sir. filaria are frequent parasites of the 
lungs of goats and sheep, and different species may be present in the same lung at one 
time {Sclilegel, "Die durch Strong, capillaris verursachte Lungenwurmseuche der Ziege," 
Arcli.f. wiss. ThierJieil., 25 Bd., 1899). The latter causes in sheep a bronchitis and 
nodular proliferating pulmonary inflammations; through the swallowing of many 
embryos inflammations of the intestine may also be produced. 

Strongylus rufescens and Str. paradoxus, Nematodium ovis pulmonalis {Lydtin), or 
Pseudalius ovis pulmonalis {Kocli) are also inhabitants of the lungs of sheep, the last- 
named causing a pseudotuberculosis. Str. commutatiis and Str. pusillus occur in the 
lungs of the hare and rabbit; Str. syngamus and hroncMalus in the trachea of birds; and 
excite inflammations. Str. micrurus {Strose, "Bau von Strongylus micrurus," Deut. 
Zeitschr. f. Thiermed., xviii., 1892) occurs in cows and calves, in arterial aneurisms as 
well as in the respiratory passages. 

Strongylus pusillus causes in cats a pulmonary disease resembling tuberculosis 
{Jeanmaire, " Ueber die hist. Verand. der Lunge bei der verminosen Pneumonic der Katze 
und des Hasen," Inaug.-Diss., Freiburg, 1900). Syngamus trachealis {Elee, "Der ge- 
paarte Luftrohrenwurm des Gefliigels," Deut. Thierdrztl. Wochenschr., 1899) is a dan- 
gerous parasite of birds, particularly of pheasants, in the trachea of which it appears 
in great numbers, and attaches itself to the mucous membrane. It is easily recognized 
by its red color. Similar to the last-named is Syngamus broncMalis, which has been 
observed a few times in geese and ducks. 

Literature. 

(Anchylostoma, ) 

Baumler: Anchylostomiasis. Correspbl. f. Schweizer Aerzte, 1881, 1885. 
Bozzolo e Pagliani: Giornale della Societa Italiana d'lgniene, ii,, Milano, 1880. 
Bugnion: Anchylostome duodenal et anemic du St. Gotthard. Rev. med, de la Suisse 
rom., i., 1881. 

Ernst: Einiee Falle von Anchylostomiasis mit Sectionsbefund. Deut. med. Woch.. 
1888. 



724 



THE ANIMAL PARASITES. 



Griesinger: Arch. f. physiol. Heilk., 1854. 

Huber: Bibliographie d. klin. Helmintliologie, Milnchen, 1893. 

Kitt: Lehrb, d. path.-anat. Diagnostik, ii., Stuttgart, 1895. 

Leichtenstem : Anchylostoma. Cbl. f. klin. Med., 1885, 1886; Deut. med. Woch., 

1885, 1886, 1887, 1888; Wien. klin. Rundschau, 1898. 
Looss: Lebensgeschichte d. Anchylostomum. Cbl. f. Bakt., xx., 1896, xxi., 1897; 

xxiv., 1898. 

Lutz: Samml. klin. Vortr. v. Volkmann, No. 255, 256, 265. , . 

Menche: Ancliylostomiasis. Zeitschr. f. klin. Med., vi. 
Olt: Wanderungen des Strongylus armatus. Cbl. f. Bakt., xxix,, 1901. 
Perroncito: Arch. p. le Sc. Med., v., Torino, 1881; Arch. ital. de biol., ii., iii., 1883. 
Prowe: Auchylostomiasis in Central America. Virch. Arch., 157 Bd., 1899. 
Schulthess: Beitrage z. Anat. des Anchylostoma. Zeitschr. f. wiss. Zool., xxxvii., 
1882. 

Sondereg-ger : Anchylostoma duodenale. Correspbl. f. Schweizer Aerzte, 1880. 
Stiles : Prevalence and Geographic Distribution of Hookworm Disease (Uncinariasis or 

Auchylostomiasis) in the United States. Bull, of Hyg. Lab., Pub. Health and 

Marine-Hospital Service of the United States. 1903. 
Ward : Nematoda. Ref. Hdb. of Med. Sc., 2d ed., vol. vi. 
Zinn u. Jacoby: Anchylostomum duodenale, Leipzig, 1898 (Lit.). 

§ 191. Anguillula intestinalis (Fig. 567) is a worm of 2.25 mm. 
length, which is found in the intestine, particularly in the tropics, and in 




Fig. —Anguillula intestinalis. Fig. 568.— Female of Anguillula stercoralis, with 

(After Braun.) eggs and embryos. (After Perroncito.) X 85. 

Italy, and has been occasionally observed in Switzerland, Germany, Bel- 
gium, and Holland (probably transported from Italy), under similar con- 



ANGUILLULA. 



725 



ditions as the Anchylostoma duodeiiale. According to the observations 
of Leuckart, Golgi, Grassi, Leichtenstern, Zinn and others, the Anguillula 
intestinalis is a hermaphrodite, the eggs of which develop even in the 
intestine to embryos of 0.2 mm. in length; and in the presence in the 
intestine of numerous parent- worms are found in the faeces in great num- 
bers. In the stools they become changed within about twelve hours into 
filaria-like larvae, which, when gaining entrance into the human intestine, 
again grow into parasitic anguillulae, which are again able to produce 
eggs capable of development. In addition there also occurs a develop- 
ment with an intermediate sexual generation, a heterogony. 

In the event of a sexual development the embryos grow outside of the 
body in about three days into sexually mature animals (female 1.2 mm. 
long, male 0.88 mm.) which are known as Anguillula or Bhabditis sterco- 
ralis (Fig. 567), and were formerly regarded as a separate species. The 
embryos of the separate sexual individuals develop into filaria-like larvae, 
which, entering the intestine of man, again grow into parasitic anguil- 
lulae. 

According to Leichtenstern and Zinn the filaria-like larvae of the 
direct development are more resistant than those of the. sexual. The 
sexual mode of multiplication occurs particularly in the anguillula, com- 
ing from the tropics, while in the indigenous form (brick-laborers of 
Germany, Belgium, Holland) the direct metamorphosis predominates. 
Leichtenstern has explained this by the assumption that the tropical 
anguillula after its transportation into a temperate zone has ada]3ted 
itself to the less favorable climatic conditions of the latter in such a 
manner that the anguillula of the temperate zone favors more the much 
simpler mode of development which is the more independent of the 
climate — namely, the direct transformation of the embryo into the filaria- 
shaped larvae, which in turn grow directly into parasitic anguillulae. 

According to the statements of various authors Anguillula stercoralis 
when present in large numbers causes diarrhoea. According to Normand, 
Grassi, Golgi, Leichtenstern, and others, the worms are found chiefly in 
the upper parts of the small intestine. According to Leichtenstern and 
Askanazy the mature animals and the larvae penetrate not only into the 
crypts of Lieberkiihn, but also into their epithelium and into the con- 
nective tissue of the mucosa, and in individual cases may break through 
the muscularis mucosae. The mother animals lay their eggs in the intes- 
tinal crypts. The embryos when hatched out wander out into the intes- 
tine. 

Literature. 

( Anguillula Stercoralis and Intestinalis. ) 

Askanazy: Invasion d, Ang. intestinalis in die Darmwand. Cbl. f. Bakt., xxvii., 1900. 
Golg-i e Monti : Sulla storia naturale delle cosi dette angiiillule stercorali e intestinali. 

Arch, per le Sc. Med., x., 1886. 
Grassi e Perona : Arcb. per le Sc. Med., xiii., 1889. 

Grassi e Segre: Nuove osservazioni sull' eterogenia del Rhabdonema (Anguillula) in- 

testiuale. Rendic. della R. Accad. dei Lincei, 1887, ref. Cbl. f. Bakt., ii., 1887. 
Huber: Bibilogr. d. klin. Helmintliologie, Suppl., Jena, 1898. 

Leichtenstern: Ang. intestinalis. Deut. nied. Woch., 1898; Cbl. f. Bakt., xxv., 1899 
Normand: Du role etiologique de I'anguillule. Arch, de med., 1878. 
Orley : Die Rhabditiden und ihre medicinische Bedeutung, Berlin, 1886. 
Pappenheim u. Braun: Ang. intest. in Ostpreussen. Cbl. f. Bakt., xxvi., 1899. 
Perroncito: Arch. p. le Sc. Med., v., 1881; Arch. ital. de biol., ii. u. iii. ; Ann. R. Ac- 
cad. di Agricoltura di Torino, xiii. ; Journ. de I'anat. et de la phys., xviii. 



726 



THE ANIMAL PARASITES. 



Teissier: Anguillule stercorale. Arch, de nied, exp., 1895. 

Thayer : On the Occurrence of Strongyloides Intestinalis in the United States. 

of Exp. Med., 1901. 
Zinn: Ueber Anguillula intestinalis. Cbl. f. Bakt., xxvi., 1899. 



Joum, 



§ 192. Tricocephalus dispar, the whipworm, iB> a commou aud rela- 
tively harmless parasite, though according to Askanazy it sucks blood 
from the intestinal mucosa. It inhabits the caecum and the neighboring 
portions of the intestine. It is found also in the domestic animals. The 

male and female are about 4-5 cm. 
in length (Fig. 569). The anterior 
body-half («, &) is very thin, thread- 
like ; the posterior, which bears the 
sexual organs (/, g, I, o, p) is much 
thicker, in the female (B) cylin- 
drical, and in the male {A) rolled up 
and provided with a spiculum (g). 

The eggs (Fig. 570) are an el- 
ongated oval, 50 /J. long, and possess 
a thick brown shell, which shows 
at both poles a peg-shaped, glassy 
swelling. 

The first stage of the develop- 
ment of the embryos takes place in 
water and in moist earth. It ad- 
vances slowly, even in summer 
lasting four to five months, and in 
the colder months of the year much 
longer. The eggs are very resist- 
ant to cold and drying. (For the 
literature see Huher, ^'^Bibliogra- 
phic der klin. Helminthologie, 
Miinchen, 1893, p. 213; Askanazy, 
^^Der Peitschenwurm," Deut. Arch, 
f. Jdin. Med., 57 Bd., 1896; Heine, 
" Anatomic d. Tricocephalus, " Ghl. 
f. Bakt, xxviii, 1900). 

§ 193. Trichina spiralis occurs 
in two forms — the trichina of the 
intestine and the trichina of the 
muscles. 

The intestinal trichina (Fig. 
571) is the sexually mature form, and is a small, white, hair-like worm 
scarcely visible to the naked eye. The female {A) is 3 mm. long, the 
male {B) is much smaller. The posterior part of the body is elongated 
in both sexes, and in the male {B) is provided on the dorsal half with 
two conical terminal pegs, which are directed toward the belly and 
are separated from each other by four knob-like papillae. Instead 
of a spiculum the muscular cloaca is protruded outward during copu- 
lation. 

The intestinal canal begins with a muscular mouth, which becoming 
wider passes into the oesophagus, which throughout its entire length is sur- 
rounded by the so-called cell-body — that is, by rows of large cells. The 
stomach, which follows the oesophagus, is a flask-shaped dilatation of the 
intestine, and is lined with finely granular cells. The stomach passes 




Fig. 569. 



Fig. 570. 



Fig. ^&%.—Tric(}ceplialm dispar. (After 
Kiichenmeister and Zurn.) A, Male; B, caudal 
end of female ; a, cephalic end ; b, anterior portion 
of body witb oesophagus ; c, stomach ; d, intestine ; 
e, cloaca ; /, seminal duct ; g, penis ; I, bell-shaped 
penis-sheath, with end of penis ; m, intestine of the 
female; ??, anus; <>, uterus; p, vaginal opening. 
X 9. 



Fig. 570.— Efig of Tricocephalm dispat 
Heller.) X 315. 



(After 



TRICHINA. 



■727 



without any essential change of structure into the intestine, which in the 
male unites with the seminal duct at the posterior end to form the cloaca. 

The testicles consist of a pouch, which begins near the caudal end as 
a blind sac, proceeds as far forward as the cell- 
bodies, and bending there, passes over into the 
seminal duct. 

The sexual organs of the female (A) consist 
of a single o\ ary, a uterus and a vagina, which 
opens externally at the junction of the first and 
second quarters. The ovary likewise forms a 
pouch lying close to the ]30sterior end of the 
body, in which the round eggs develop. The 
pouch passes anteriorly into the sac-shaped uterus. 

The eggs develop within the uterus into em- 
bryos which are set free at birth. 

The muscle=trichina (Fig. 572) is a worm 
0.7-1 mm. in length, which lives in the muscles 
of the body. It is usually rolled into a spiral 
and lies in a capsule, which occasionally contains 
lime -salts. Between the coils of the worm there 
is a finely granular mass. 

A single caj^sule may contain three to five 
trichinae. 

If a piece of muscle containing living tri- 
chinge is taken into the stomach of a host— for 
example, man — the capsule is dissolved and the 
trichinae are set free. In the intestinal canal they 
attain sexual maturity within two and a half days, 
when copulation takes place. On the seventh day 
after the ingestion of muscle trichinae the birth 
of embryos begins, which continues some time, 
even for weeks. A single female trichina may 
bear from one thousand to thirteen hundred 
young. According to Pagenstecher, Chatin, Cer- 
fontaine, and Askanazy, the female trichinae pen- 
etrate into the intestinal villi and deposit the 
embryos in tlie chyle -vessels, whence their migra- 
tion begins. To what extent they are swept along 
passively by the lymph, or to what extent active 
migration is concerned in their spreading, is a 
difficult matter to determine. When arriving in 
the muscles they penetrate the primitive fibres, 
bring the adjacent contents of the fibre to degen- 
eration, and grow in about fourteen days to fully 
developed muscle trichinae. In the neighborhood 
of the trichinae there occurs a proliferation of 
the muscle-nnclei and an inflammation of the 
connective tissue. At first the muscle -trichinae 
are enclosed only by the sarcolemma, which ap- 
pears thickened and liy aline about them. Later 
there occurs in the neighborhood an inflammatory 
proliferation of granulation tissue which leads to 
the production of connective tissue on the outside 
of the sarcolemma and penetrates even within the 



Fig. 571.— Sexually mature 
trichinae. A, Female; B, 
male. (After Leuckart.) 
X 120. 



728 



THE ANIMAL PARASITES. 



sarcolemma tube, the muscle -nuclei being destroyed. Fat cells may 
appear later iu the conuective tissue of the capsule, the development of 
the latter being especially marked at the poles. 

The intestinal trichinae have a limited life of from five to eight weeks. 
The muscle-trichinae, on the other hand, may live for a very long, possi- 
bly an unlimited time— that is, until the death of the affected individual; 
or at any rate for years, although, according to Ehrhardt, a few may die 




Fig. 572. — Encapsulated nmsde tricbinie. (After Leuckart.) X 60. 



before the encapsulation. After some time there frequently occurs a 
deposition of lime-salts in the capsule, especially at the poles, causing it 
to appear glistening-white by reflected light, and cloudy and dark by 
transmitted light. In rare cases the trichinae after dying also become 
c^ilcified. 

Trichinae have been observed, besides in man, also in the hog, cat, 
dog, rat, mouse, marmot, polecat, fox, marten, badger, hedgehog, and 
raccoon. Through the feed ng of trichinous meat muscle-trichinae may 
also be developed in rabbits, guinea pigs, sheep, dogs, etc. Man becomes 
infected through the eating of uncooked pork. The invasion of the tri- 
chinae produces various phenomena in man. The introduction of trichin- 
ous meat into the intestine is followed by the symptoms of an intestinal 
catarrh. With the invasion of the muscles there are produced pain, 
swelling, oedema, paralysis, and not infrequently fever. The symptoms 
are most severe in the fourth and fifth weeks. Death not infrequently 
results. 

The trichinae are found most abundantlj^ in the diaphragm, tongue, 
intercostal muscles, the muscles of the neck and larynx, the lumbar mus- 
cles, and are scattered most sparsely in the distant muscles of the extremi- 
ties. They are usually most numerous about the insertions of the 
tendons. 

Literature. 

( Tr^ichina SinraUs ; TriGhinosis. ) 

Askanazy: Znr Lebre von der Trichinose. Cbl. f. Bakt., xv., 1894; Viicli. Arch,, 
141 Bd., 1895. 

Cerfontaine: Contr. a I'et. de la tricliiuose. Arcli. de biol., xiii., 1893; Cbl f. Bakt., 
xxi.. 1897. 

Chatin: La triebine et la tricliinose, Paris, 1883. 



FILARIA. 



729 



Ehrhardt: Muskelveranderungen bei Trichinose. Beitr. v. Ziegler, xx., 1896. 
Graham: Naturgesch. d. Trichina spir. Arcli. f. mikr. Anat., ]., 1897. 

Hertwig: Entwickelung d. Trichinenkapsel. Miinch. med. 

Wocli., 1896. 
Johne: Der Tricbinenschaiier, Berlin, 1888. 
Langerhans: Ueber regressive Verand. d. Trichinen u. ibrer 

Kapseln. Vircb. Arcb., 130 Bd., 1892. 
Lewin: Zur Diagnostik u. patb. Anat. d. Tricbinose. Deut. 

Arcb. f. klin. Med., 49 Bd., 1893. 
Riess : Tricbinenkrankbeit. Eulenburo^'s Realencyklop., 
xxiv., 1900. 

Soudakewitscli : Modific. des fibres rauscul. par la tricbinose. 

Ann. de I'lnst. Past., vi., 1892. 
Stiles : Tricbinosis in Germany. Bull. 30, U. S. Bureau of 

Animal Indus., 1901. 
Virchow : Die Lebre von den Tricliinen, Berlin, 1866. 
Volkmann: Tricbinose. Beitr. v, Ziegler, xii., 1894, 
Williams: The Frequency of Tricbinosis in tbe United 

States. Jour, of Med. Res., 1901. 
Zenker: Vircb. Arcb., 18 Bd. ; Deut. Arcb. f. klin. Med., 
viii. 



Fig. 573. 

Fig. 57'S. — Filaria sive Dracunculns medinensis. 
(After Leuckart.) Natural size. 

Fig. 574.— Embryo of Filaria Bancrofti, known 
as SVaria sanguinis hominis. (After Lewis.) X 400. 



§ 194. Filaria or Dracunculus medinensis, the 

Guinea-worm (Fig. 573), is a thin, thread-like 
female worm from 60 to 100 cm. in length. The 
males (observed by Charles) which were attached 
to female filarise, were only 4 cm. long. The an- 
terior extremity is rounded off, while the posterior 
tapers into a pointed tail which is curved toward 
the belly. The external cover- 
ing consists of a firm cuticle, 
which at the cephalic end is 
thickened in the form of a 
shield. The intestinal canal is 
narrow and has no anus. The 
uterus, filled with young, takes 
up nearly the whole of the body- 
cavity. The embryos, which are 
set free by the bursting of the 
mother- worm, have a firm cuticle 
and an awl-shaped tail. As in- 
termediate host, the embryos 
seek out small crustacese, in 
which they are probably taken 
into the stomach of man with 
the drinking-water. In Afiica 
and Asia the worm is of fre- 
quent occurrence. It develops 
in the skin to sexual maturity 
and causes abscesses of the af- 
fected region. It is usually 
found on the lower extremities, 
especially in the region of the 
heels. 

Filaria sanguinis hominis is 

the name given to the larvce (Fig. 
574) of a worm, which occur in 
the blood and lymph of man, 




780 



THE ANIMAL PARASITES. 



and are about 0.35 mm. in length. The sexually mature worm is fili- 
form, the male about 15 em. long and the female 8 cm. It is called 
Filaria Bancrofti after its discoverer. The worm inhabits the lymj)h- 
vessels, particulai ly those of the scrotimi and lowei- extremities, and may 
be present in large numbei s. It causes lymph-stasis and inflammations 
wliicli lead to swcllijif/s offhr J i/ni ph -gJ(ut(ls nud to eleplianUasis-like thicl'en- 
iiKj of t lie tissue, associated witli (cdeiiia and lymphangiectasis. Purulent 
intianmiations, lymph-abscesses, buboes, chylous hydrocele, and chylous 
ascites may api^ear in consequeiu-e of its presence. 

Fi'om the lymphatics of the limbs and scrotum the eggs and embryos 
(0.35 mm. long) (Fig. 574) pass into pnrts of the lymi)hatic system and 
into the blood, giving rise to lueniaturia, chyluria, and chylous diarrhoea. 
According to 3Ianson and Scheube the tilarite are present in the blood 
taken from the skin only during the night ; von Linstow explains this 
phenomenon as due to the fact that during sleej) the peripheral vessels 
become dilated, and so permit the entrance of the filarise, while the cap- 
illaries, being narrower during the day, do not permit such entrance. 
The ha^maturia is tlie result of the collection of embryos in the blood- 
vessels of the urinary tract. The chyluria and the chylous diarrhoea, on 
the other hand, ai-e due to the obstruction by the parasites of the thoracic 
duct, thus causing a lymph -stasis which extends to the lymphatics of the 
bladder and intestine and there occasions the escape of lymph. Accord- 
ing to Scheube the rupture of the lymphatics is also attended by a rupt- 
ure of blood-vessels, so that blood becomes mixed with the lymph. The 
embryos may pass out from the urinary api^aratus through the urine. 

The distribution of the embryos is, according to Manson, accomplished 
by means of mosquitos, which take up the parasite during the act of blood- 
sucking. In the mosquitos they pass through a second stage of develop- 
ment and are then (James) after two or three weeks ready for the infec- 
tion of a new host. Manson formerly held the opinion that they entered 
the water, and in a free condition Avere taken up in the water into the 
intestinal tract. The investigations of James, Low, Grassi, and^^"oe, who 
followed their development and migration in the body of mosquitos, 
make it seem probable that they are transmitted to a new host through 
the bite of the mosquito. 

The Filaria sanguinis occurs, so far as is known, only in the tropics 
(Brazil, Egypt, Algiers, Madagascar, Zanzibar, Soudan, South China, 
Calcutta, Bahia, Guadeloupe). 

Mackenzie estimated the number of lilaria-embryos present in the total bulk of the 
blood of a case of Juematochyluria closely studied ^by him at from thirty-six to forty 
millions. The patient died from empyema; during the disease the filariae died. 

In the domestic animals numevoufi f la ri a -species occur and inhabit different parts 
of the body. Filaria painUuxa is a common parasite of the horse, donkey, and cattle; 
it lives in the serous cavities and reaches a length of from 5-18 cm. Filaria hcematica, 
a worm 13-15 cm. long, inhabits the right heart and the pulmonary artery of the dog, 
and in this situation gives oft' its embryos to the blood-stream. It occurs particularly 
in America, China, and India. 

Literature. 

(Filaria.) 

Earth: De la filaire du sang et ses rappoits avec Telephantiasis des Arabes et qiielques 

autres maladies des pays chauds. Ann. de derm, et syph.. 1881. 
Clanchard: Filaria loa. Arch, de parasitol., ii., 1899. 

Charles : History of the Male of Filaria Medinensis. Scient. Mem. Med. OtHcf Army 
of India, vii.. Calcutta, 1892. 



ARTHROPODA. 



731 



Pirket: De la filarosc du sang. Accad. R. de med. de Belg., Bruxelles, 1895. 
Goetze : Die Chylurie, Jena, 1887. 

Grrassi : Filaria inermis, ein Parasit des Menschen, des Pferdes u. des Esels. Cbl. f . 
Bakt., i., 1887; Entwickelungscyclus von 5 Parasiten des Hundes (Taenia cucu- 
merina, Ascaiis marginata, Spiroptera sanguinolenta, Filaria immitis Leidy und 
Haematozoon Lewis). Ibid., iv., 1888; Hgematozoon Lewis (Filaria des Hundes). 
lb., vii., 1890. 

Grassi u. Noe: Uebertrag. d. Blutfllaria durch Stechmiicken. Cbl. f. Bakt., xxviii., 
1900. 

Havelburg-: Ueber Filaria Sanguinis und Chylurie. Virch. Arcb., 89 Bd., 1882. 
Huber: Bibliograpbie d. klin. Helminthologie, Suppl., Jena, 1898. 
James : On the Metamorphosis of Filaria sanguinis in Mosquitoes. Brit. Med. Journ. , 
ii., 1900. 

Laveran et Blanchard : Les vers du sang, Paris, 1895. 

Lewis: Geschlechtsreife Form der Filaria sanguinis. Cbl. f. d, med. Wiss., 1877. 

V. Linstow: Ueber Filaria Bancrofti Cobbold. Cbl. f. Bakt., xii., 1892. 

Liothrop and Pratt: Two Cases of Filariasis. Amer. Journ. of Med. Sc., cxx., 1900 

(Lit). 

Low: Filaria uocturua in culex. Brit. Med. Journ., i., 1900. 

Mackenzie, St. : Transactions of the Pathological Society of London, 1892. 

Manson: The Filaria Sanguinis, London, 1883; The Filaria Sanguinis Hominis Major 

and Minor, Two New Species of Hsematozoa. Lancet, 1891; ref., Cbl. f. allg. 

Path., ii., 1891. 

Murata: Zur Kenntniss der Chylurie. Mittheil. d. med. Fac. der Universitat, Tokio, 
1888. 

Rieck: Filaria immitis u. ihre Embryonen im Blute v. Hunden. Deut. Zeitschr. f, 

Thiermed., xiv., 1889. 
Scheube : Die Krankheiten der warmen Lander, Jena, 1900. 
Sonsino: The Life-history of Filaria Bancrofti. Brit. Med. Journ., i., 1900. 



III. Arthropoda. 

1. Aradinida. 

§ 195. The parasites included among the Arachnida are chiefly epizoa^ 
which either temporarily or permanently inhabit the skin. Only one 
species — Pentastoma — occurs in the larval 
form within the tissues. The most com- 
mon parasites of this group belong to the 
Mites {Acarina). The pentastoma be- 
longs to the family of tongue -worms 
{Pentastomidw or lAnguatuUdce). 

(1) Acarus scabiei or Sarcoptes 
hominis, the itch=mite, is a parasitic 
mite the size of a pinhead with a turtle- 
shaped body, provided on the ventral 
surface both anteriorly and posteriorly 
with two pairs of legs, each of which is 
furnished with bristles (Fig. 575). The 
anterior pairs of legs extend out into 
pedicled cliuging-discs. The same ar- 
rangement is found in the posterior two 
pairs in the male, while in the female 
both of the posterior pairs end in long- 
bristles. Several bristles are also found 57.5.-FemalP itcH-inite, ventral sur- 

along the border of the posterior portion fa* 4^). 

of the body, while the back is studded 

with tooth-like knobs. The head is round and likewise set with bristles. 
The female is nearly double the size of the male. 




■732 



THE ANIMAL PARASITES. 



The mite lives in the epidermis (Fig. 576, a, d) in which it forms 
burrows, some of which are 10 cm. long. 

In the burrows the female (d) lays the eggs, which develop in situ 
into the young itch-mites (e), which penetrate still deeper into the epi- 
dermis, and after repeated sheddings of their skins grow into sexually 
mature animals. The skin responds to the irritation produced by the 



^ e 




Fig. 576.— Scabies (alcohol, carmine) . a. Homy layer of the epidermis, perforated by numerous bur- 
rows of the itch-mite ; mucous layer, and papillary body, the latter greatly enlarged and infiltrated 
with cells; c, cutis infiltrated with cells; (7, section" through a fullv developed itch-mite; e, eggs and 
embryos of different sizes ; f, faeces. X 20. 

presence of the mites by an increased production of epithelial cells (a) 
and inflammation (c). The latter is still further increased through the 
scratching of the spots which itch in consequence of the invasion. 

2. Leptus autumnalis, the harvest-mite (Fig. 577) is the red-colored 
larva of a variety of Trombididce, which lives upon grasses and bushes 
and upon grain, and when occasion offers alights upon the skin of man, 
where it penetrates The epitheliimi and causes itching and inflammation. 

3. Demodex or Acarus folliculorum hominis (Fig. 578) occurs either 
singly or in numliers in tlie hair-follicles of the face, as well as in the 
ducts of the sebaceous and Meibomian glands. Hausche found the de- 
modex on the eyelashes in seventy-nine per cent., and Joers in sixty-four 
per cent, of the cases examined. Children under one year of age were 
free. The female is 0.4 mm. long, the male 0.3 mm. The eggs are de- 
posited upon the shaft of the hair or upon any other portion of tissue, and 
develop after two sheddings into sexually mature animals which are found 
in the entrances to the hair -follicles and sebaceous glands, with their heads 
directed inward. The assumption that the demodex causes inflammation 
(acne, blepharitis acarica) is not supported (Joers, Hausche), since in 
spite of its presence in the great majority of cases signs of inflammation 
are wanting. 

It is about 0.3 mm. long, and has on its anterior ventral surface four 
pairs of short thick feet. The head possesses a snout and two feelers. 

4. Ixodes ricinus, the wood-jacl- or wood-ticJc (Fig. 579) is a fairly 



PENTASTOMA. 



733 



large yellowisli-browu member of the Arachnida belonging to the ticks. 
It has a black head provided with a sucking apparatus, and a very dis- 
tensible leathery body. It is of common occurrence upon grass and 
bushes, and sometimes alights upon man or beast. By means of it« 
sucking apparatus it draws blood from the skin and swells up to a very 
remarkable extent. 

5. Pentastoma denticulatum is the lar\ a of Pentastoma tsenoides, 
a lancet-shaped animal belonging to the tongue-worms or Pentustomidce. 
It inhabits the nasal, frontal, and maxillary cavities of various animals, 
especially of the dog, very rarely of man (Laudon) and occasions inflam- 
mations. The female of the mature animal is 50-80 mm. long, and an- 
teriorly from 8-10 mm. broad ; the male is 16-22 mm. long, and anteriorly 
from 3-4 mm. broad. The body consists of eighty-seven to ninety seg- 
ments, the most anterior of which bear lateral segment-appendages, the 
pairs of limbs. The eggs, which are produced in very great numbers, 
are oval. The larva is 4-5 mm. long, 1.5 mm. broad, plump, flattened, and 
inhabits chiefly the liver, lung, or spleen, or more rarely the other organs 
of man and the herbivora. It occurs in the form of a small nodule encap- 
sulated in connective tissue. The body consists of about fifty ring-shaped 
segments which are provided at the borders with spines (Fig. 580), and 




Fig. 577. Fig. 578. Fig. 580. 



Fig. 577.—Leptmautumnalis. (After Kiichenmeister and Zurn.) 

YiG. 678 —Acarus folliculorum liominis. (After Perls.) X 300. 

Fig. 57d.— Ixodes ricinus, sucked half full of blood. X 2. 

Fig. 580.— Cephalic end of Pentastoma denticulatum. (After Perls.) X 40. 

the cephalic end is provided with four hook-shaped feet. The eggs are 
taken in from the external world through the intestinal tract. The para- 
sites set free in the intestine wander by means of a boring apparatus 
through the mesentery into the mesenteric lymph-glands, or penetrate 
directly into the blood-vessels, and are carried by the blood-stream 



734 



THE ANIMAL PARASITES. 



to the liver or even to the lungs, where after shedding they de\'elop 
into the encysted larvae. The larvae may in their wanderings gain access 
to the nasal cavity of their host, and develop into mature animals, al- 
though the further development usually takes place only after their re- 
ception into a new host. 

According to the published reports of Tanaka a small red jnite occurs in great 
numbers in different parts of Japan during midsummer, and clinging tirmly to the skin 
of man causes the so-called Kedani-disease, which is ctiaracterized by inflammation of 



Fig. 581.— Male of Dcnnatop]iayiu< commimis seen from the veutral side. (After Putz.) X 50. 
Fig. 582. — Male of DermatoMptes communU, seen from the ventral side. ' After Piitz.) X 50. 

the skin and lymph-glands, with high fever, and often ends fatally. It is probable that 
these symptoms are due to secondary infections (proteus and streptococci) in the bites 
of the mite. 

In the domestic animals living mites occur very frequently as parasites of the 
skin, and represent different species of various families. 

Sarcoptes liominis, the hurroic-mite or itch-mite of man is found also in horses and 
Neapolitan sheep. In addition still other different species of sarcoptes may be distin 
guished as parasites of the domestic animals— for example, Sarcoptes sqvamiferus in dogs, 
hogs, sheep, and goats, and Sarcoptes minor in cats and rabbits. 

Bermatophagiis, the devouring-mite (Fig. 581), with a broad head, occurs in different 
animals, and different species may be accordingly distinguished. They live upon the 
cells of the epidermis and cause a desquamation of the skin. 

Dermatocoptes, the sucling-rnite (Fig. 582), with long narrow head, takes blood and 
lymph from the skin aiul causes inflammation. Dermatocoptes communis occurs in 
horses, cattle, and sheep.. JJevtnatocopjtes cunicv.li is a parasite of the rabbit's ear. 

Syrnhiotes eqid of Oerlach is a mite which occurs chiefly upon the feet of the heavy 
English and Scotch horses, and causes a moist dermatitis, often incorrectly called m.a- 
landers. 

Dermanyssus amiim is a long, red, blood-sucking mite, about 1 mm. long, and is 
often found upon birds. 

Of the tick family there occur on dogs, cattle, and sheep different species of Ixodes, 
on pigeons Argas reji.exus, and others, Argas 7^eflexus can. according to D'Aj^itolo, occur 
also on man. 

Leptus autmnnalis occurs also on dogs and chickens. 

Different species of Demodex occur in dogs and swine, and cause pustular erup- 
tions. 

Pentastomata occur also in cattle, sheep, and goats, and in certain regions are very 
common in the first named. 




Fig. 581. 



Fig. 582. 



INSECTA. 



T35 



2. Insectu. 

§ 196. The parasites belonging to the class of Insecta are f oi* the greater 
part epizoa. In part they are but transient inhabitants of the skin, 
deriving from it their nourishment; in part they are permanent inhabi- 
tants and utilize the skin structures for the deposit of their eggs. Of the 
numerous species belonging to this class the following may be mentioned: 

(1) Pediculus capitis, the head-louse (Fig. 583), inhabits the hairy 
portions of the head, and derives its nourishment (i.e., blood) from the 
skin, by means of its feeding apparatus. Its eggs (nits) are barrel-shaped 
and white, and are attached to the hairs by means of a chitinous shell. 
The embryo hatches in about eight days. In consequence of the scratch- 
ing induced by the itching there often arise inflammations of the skin, in 
particular eczemas, which are often relatively severe. 

(2) Pediculus pubis, the felt or crdb-louse (Fig. 584), inhabits the 
hairy parts of the trunk and extremities. Its habits of life are the same 
as those of Pediculus capitis. 

(3) Pediculus vestimentorum, the clothing or hody-louse (Fig. 585), 
lives in the wearing ax)i)arel, and lays its eggs in the same. It gets 
upon man to obtain its nourishment. 

(4) Cimex lectularius, the bedbug, dwells in beds, floors, closets, etc. 
During the night it gets upon man to suck blood. It causes wheals in 
the skin. 

(5) Pulex irritans, the common flea, also draws blood from the skin. 
At the point where it has sucked there is found a little punctate haemor- 




FlG. 583. Fig. 584. Fig. 585. 



Fig. 583.— Female of Pediculv^ capitis, seen from the ventral surface. (Kiicbenmeister and Ziim.) X 13. 

Fig. 584.— Male of Pediculus pubis, seen from the ventral surface. (Kiichenmelster andZurn.) X 13. 

Fig. 585.— Female of PedicuTufi vestimentorum, seen from the ventral surface. (Kiichenmelster and 
Zurn.) X 9. 

rhage. Occasionally it causes wheals and swellings. It lays its eggs in 
the cracks of floors, in sawdust, etc. 

(6) PuSex penetrans, the sand flea, occurs in South Africa in the 
sand. The female lays her eggs in the skin, thereby causing an intense 
inflammation. 

(7) Mosquitos provided with stinging and sucking ai)paratus (CuUci- 
dce and Tipulidce), horse=flies (Tabanidce), and flies (Stomoxyidce) draw 
blood frequently from the skin of man. Various flies (CEstridce or biting 



736 



THE ANIMAL PARASITES. 



flies, Muscidce or blow-flies) occasionally lay their eggs in the skin, in ulcers, 
or wounds, or in the accessible body -cavities, in consequence of which 
the maggots developing cause local destruction of tissue and inflammation 
(myiasis). Under certain conditions their larvae may get into the intesti- 
nal tract with the food and there undergo further development (myiasis 
intestinalis). This is especially likely to occur when abnormal conditions 
which interfere with digestion are present in the stomach and intestine. 

The eggs of the Muscidce (in Europe 
usually of SarcopMlia Wohlfarti, 
in America of Compsomyia or 
Lucilia macelJaria and Musca an- 
thropophaga) , when laid upon the 
mucous membranes or in wounds, 
hatch after a few hours, and cause 
destruction of the neighboring 
soft parts through their efforts to 
obtain nourishment. In the au- 
ditory canal, nose, and antrum of 
Highmore, the bones may be laid 
bare (myiasis mucosa). In the 
course of about a week the larvae 
leave the ulcers and pass into the 
pupa stage in the earth. The 
(Estridce (in Europe, Hypoderma 
bovis and Hypoderma Diana ; in America, BennatoMa noxialis or Cuterehra 
cyaniventris) lay their eggs upon wounds or in the intact skin. The 
larvae, hatching very soon, penetrate into the cutis by means of their 
hooklets, and after several sheddings grow in from one to six months into 
larger larvae about 2 cm. long. They cause, particularly in their later 
stages, painful swellings of the neighboring tissue (myiasis cestrosa). 

Eegarding the significance of different species of AnojyJieles as conveyers 
of malarial infection see § 182. 





Fig. 



5^.—GaUrop?uliiS eqxd. 

Male; larva 



(After Brauer. 



Parasites belonging to the Muscidm and (Estridce play a more important role in the 
case of the domestic animals than in man ; and the larvae of the species of CEstrus in 
particular occur as parasites in animals. For example, the larvae of GastropMlus equi 
(Fig. 586), Gast. pecorum and Gast. hcemorrhoidaUs inhabit the stomach and adjacent 
portions of the intestinal tract of the horse, where they complete their development up 
to the pupa-stage, when they leave the animal. 

CEstrus ovis lays its larvae in the nasal cavities of sheep, whence they may wan- 
der, under certain conditions, into the frontal, nasal, and maxillary cavities, or even 
into the cranial cavitj^, and excite inflammation. 

The larva of Hypoderma or (Esirus hovis is 5-15 mm. long. It inhabits the skin and 
spinal canal of cattle, completing its development up to the pupa-stage, at which time 
it leaves the animal. According to SchneidemuM the larvae do not always enter through 
the skin, but are more often taken in with the food, whereupon they penetrate through 
the wall of the oesophagus toward the skin and spinal canal. The latter follows from 
the fact that they are found in the wall of the oesophagus from October to January, 
and under the sliin, on the other hand, from January to April. 



Literature. 

(Parasitic Arachnida and Insecta. ) 

D'Ajutolo: Deir argus reflexus parasita dell' uorao. Mem. della R. Accad. di Bolog- 
na, viii., 1899. 
Brauer: Monographic der Oestriden, Wien, 1863. 

Csokor: Ueber Pentastomen u. Pentastoma denticulatum aus d. Leber des Pferdes. 
Zeitschr. f. Veterinark., i., 1887; Cbl. f. Bakt., i., 1887. 



THE ANOtAL PAKASITES. 



Dubreuilh: Les dipteres cuticoles chez rhomme (Lit.). Arch, de med. exp., 1894; 

Dermatozoaires. Paris. 1900. 
Hausche; Demodex folliciilonim im Aiigenlidc. jNIlinch. med. Wocli., 1900. 
Hoffmann: Fliegenlarveu im mensclil. Magen. Munch, med. Woch., 1888. 
Huber: Bibliographic d. klin. Entomologie, i.-iv., Jena, 1898-1900. 
Joers: Acarus folliciilorum u. s. Bez. z. Lidrandenztiindung. Deut. med. Woch., 

1899. 

Josepli: Ueber d. Fliegeu als Schadlinge u. Parasiten d. Menscheu. Deut. Medicinal- 

Zeit., 1887; Ueber Mjiasis externa dermatosa. Monatsh. f. prakt. Derm., 1887. 
Kitt: Lehrbuch d. path.-anat. Diagnostik, i., Stuttgart, 1900. 

Kulagin: Naturgeschichte des Pentastomum denticulatum. CbL f. Bakt., xxiv., 
1898. ^ 

Lallier: Etude sur la myase du tube digestif, Paris, 1897 (Lit.). 
Lampa: Fliegenmaden im Darm des Menschen. Cbl. f. Balvt., iv., 1888. 
Leuckart: Bau u. Entwickelungsgeschichte des Pentastoma, Leipzig, 1880. 
Iiublinski: Fliegenlarven im meuschl. Magen. Deut. med. Woch., 1885. 
Majocclii: Demodex folhc. nelle ghiand. Meibom. Arch. p. le Sc. Med., 1899. 
Nuttall : Insects, Arachnids and Myriapods as Carriers of Disease. Johns Hop. Hosp. 
Kep.. 1899. 

Osborne: Insects Affecting Domestic Animals. XJ. S. Dept. of Agric. Bull., 1896, 
Peiper: Fliegenlarven als gelegentl. Parasiten d. Menschen, Berlin, 1900. 
Rahlmann : "Blepharitis acarica. Deut. med. Woch., 1892; Monatsbl. f. Augenheilk., 
1899. 

Salmon and Stiles: Sheep Scab, Washington, 1898. 

V. Samson-Himmelstierna : Ein Hautmaulwurf. Arch. f. Derm., 41 Bd., 1897. 
Sandabl: Ueb. d. Yorkommen v. Insecten im menschl. Organismus. Cbl. f. Bakt., 
v., 1889. 

Scbeube: Die Krankheiten d. warmen Lander (Sandfloh, Fliegenlarven), Jena, 1900. 
Sciscbka: Anatomic der Scabies. Arch. f. Derm., 53 Bd., 1900. 
Schneidemiilil : Entwickelungsgesch. d. Bremsenlarven. Cbl. f. Bakt., xxii., 1897. 
Schoyen: Ueber das Vorkommen von insecten am menschl. Korper, Biol. Cbl,, iv., 

1885. 

Shipley: Revision of the Linguatulidie. Arch, of Parasit., 1898. 

Sommer: Pentastomum denticulatum. Eulenburg's Realencyklop., xviii., 1898 (Lit.). 

Tanaka: Aetiologie u. Pathogenese d. Kedani-Krankheit. Cbl. f. Bakt,, xxvi., 1899. 

Ward: Arachnida. Ref. Handb. of Med. Sc., 2d ed., vol. i. 

Wilms: Myiasis dermatosa oestrosa. Deut, med. Woch., 1897. 

(Animal Farasites.) 

Blanchard: Parasites animaux. Traite de path. publ. par Bouchard, ii., 1896. 
Braun: Die thierisclien Parasiten des Menschen, Wiirzburg, 1895. 
Davaine: Traite des entozoaires, Paris, 1877. 

Huber; Bibliographic der klin. Helminthologie, Miinchen, 1891-98; Bibliographic der 

klin. Eutomologie, i.-iv., Jena, 1898-1900. 
Kuchenmeister u. Ziirn: Die Parasiten des Menschens, Leipzig, 1882. 
Leuckart: Die menschl. Parasiten, Leipzig, 1863-76; 2te Aufl., 1879-1901. 
Moniez: Traite de parasitologic, Paris, 1896. 
Miiller: Statistik der menschl. Parasiten, Erlangen, 1874, 

Neumann : Traite des maladies parasitaires des animaux domestiques, Paris, 1888, 
Parona: L'Elmintologia Italiana, Genova, 1894 (Lit, bis z. J., 1890), 
Perroncito: I parassiti dell' uomo e degli animali utili, Milano, 1882, 
Stein: Die parasitaren Krankheiten des Menschen, i., Lahr, 1882, 
Ward: Articles on Parasites, xVrachnida. Nematoda, etc, in Ref. Handb. of Med. Sc., 
2d ed, 

Zschokke, F. : Rech, s. 1 'organisation des vers parasites des poissons d'eau douce, 
Paris, 1885. 

Ziirn: Die Krankheiten d. Hausgeflligels, Weimar, 1882; Die Schmarotzer auf und in 
dem Korper unserer Haussiiugethiere, i., Weimar, 1883-89. 

39 



GENERAL INDEX. 



Abdominal cavity, faulty closure of, £ 
Abortion, 496 
Abrachius, 516 
Abrin, poisoning by, 27 
Abscess, 385, 574 

burrowing, 363 

chronic, 363 

cold, 621 

congestion, 363 
Abscess-membrane, 353 
Acardiacus aceplialus, 532 

amorphus, 532 

pseudoacormus, 532 
Acarina, 731 

Acarus folliculorum hominis, 732 

scabiei, 731 
Acervuloma, 430 
Acervulus cerebri, 223 
Achirus, 519 

Achorion Schonleinii, 675 
Achromatopsia, 55 
Achyla prolifera, 678 
Acids, corrosive, 22 
Acme of a fever, 94 
Acne, 574 

Aconitine, poisoning by, 29 
Acrania, 504 

origin of, 507 
Acromegaly, 212, 263 
Actinomyces or ray-fungus, 649 
Actinomycosis, 649 
Acuminate condyloma, 362 
Addiment, 118 
Addison's disease, 89 

pigmentation of skin in, 232 
Adenocarcinoma, 463 

development of, 455 
Adenocystoma, 442, 485 

papillary, 446 
Adeno-cysts, 477 
Adenoma, 437 

alveolar, 440 

carcinomatosum, 458 

conversion of, into a carcinoma, 455 

destruens, 458 

malign um, 458 

papillary, 440 

tubular, 440 

umbilical, 513 
Adenomata and carcinomata, difficulty of 

distinguishing between, 441 
Adenomyoma, 405, 477 
Adenomyosarcoma, 485 



Adenosarcoma, 468 

Adipose tissue, atrophy of, 193 

development of, 290, 291 

patholog}"" of. 193 
Adipositas, 52, 191 
^gagropilae, 226 
Equatorial plate, 273 
Aerobes, 543 

Age, predisposition in old, 50 
Agenesia, 178 

partial, of the cranium, 504 
Agglutination of colon bacillus, 594 

of typhoid bacillus, 109, 592 
Agglutinins, 110 
Agnathia, 509 
Agrotis segetum, 678 
Air, entrance of, into the right heart, 71 

embolism, 71 
Albinism, 250 

Albuminoid bodies, protective, 105 

Alcohol, poisoning by, 28 

Alexins and immunitoxins, 118, 119 

protective. 105, 106, 118 
Alkaloids, toxic cadaveric, 38, 41, 549 

vegetable, 18 
Algor mortis, 167 
Alveolar sarcoma, 420 
Amelus, 516 
Amides, 542 
Amido-acids, 542 
Amins, 542 

Amitotic nuclear division, 276 
Amme, 700, 708 

Amnion, pathological conditions of, 490 
Amniotic adhesions a cause of malforma- 
tions of the embryo, 490 
Amceba coli felis, 681 

coli mitis, 680 

coli vulgaris, 680 

dysenterise, 680 
Amphibolous stage of fever, 94 
Amphimixis, 61 
Amputation neuroma, 302, 411 
Amyelia, total or partial, 499 
Amyloid concretions, 214 

degeneration, 208 

local infiltration of, 213 
Anabiosis, 11 
Ansemia, 129 

chronic, 126 

collateral, 133 

due to tapeworm, 718 

general, 136 



740 



GENERAL INDEX. 



Anaemia, localized, 129, 132 
Anaerobes, 543 
Anaplasia, 4.i)8 
Anasarca, 150 

Anatomy, general pathological, 3 
Ancliylostoma duodenale, 721 

Americana, 721 
Androgynes, 527 
Anencephalia, 504 

origin of, 507 
Anencephalus, total, 505 
Aneurism, cirsoid, 397 
Angioma, 393 

arteriale plexiforme, 397 

artcriale racemosnm, 397 

caveruosiim, 395 

tissiiral, 394 

liypertrophicum, 397 

lympliaticum, 399 

plexiforme arteriale, 397 

simplex, 393 

venosum (varicosum), 395 
Angiomyoma. 405 
Angiosarcoma. 424 
Anguillula intestiualis, 724 

stercoralis. 725 
Anliydriemia, 126 
Aniline, poisoning by. 27 
Animal diseases caused by cocci, 579 

parasites. 45, 680 
Anopheles, 695 
Antagonism, bacterial, 545 
Anthrax-bacilli. 584 

attenuation of. 588 
Anthrax, protective inoculations against, 
588 

symptomatic. 656 
Autia'utolvsin. 119 
Antibodies. 109, 115 
Antitoxins. 106. 109. 114. 115. 118 

of diphtheria, 117 
Anus, condyloma latum of the, 633 
Aphthre. 672 
Aplasia, 165 
Aprosopia, 508 
Apus. 516. 519 
Apyrexia. 95 
Arachnida, 33, 46. 731 
Area cerebroyasculosa. 505 

medulloyasculosa, 500 
Are:as reflexus, 734 
Argyria. 249 
Arrhiuencephalus. 506 
Arsenicismus, pigmentation in. 242 
Arseniuretted hj'drogen, poisoning by, 26 
Arterioliths, 146 
Arteriosclerosis, 216 
Artery, obliteration of, 148 

terminal. 160 
Arthritis urica, 224 
Arthropoda, 731 

parasitic. 33. 46 
Ascaris lumbricoides, 720 

megalocephala. 720 

mystax, 720 
Ascites, 151 

chylous, 164 



Ascococci. 540. 559 
Asiatic cholera, 660 
Aspergillus flayescens or flayus, 671 

fumigatus, 671 

nidulans, 671 

niger, or nigricans, 671 
Aspergillus-mycoses, 673 
Asphyxia. 6 

local, 170 
Astrocyte, 300 
Atavism. 58 
Atheroma. 252 

Atmospheric pressure, effect of an in- 
crease of, 13 

effects of sudden lowering of, 12 
Atresia ani, 515 

ani vesicalis. 516 

ani urethralis. 516 

ani uterina, 516 

ani vaginalis, 516 

oris, 509 

recti, 515 

urethrcT, 515 
Atrophy, 182 

active. 185 

bro^yn, 183 

degenerative, 184 

disuse, 187 

cxcentric, 183 / 

neuropathic, 187 

passive, 185 

pigment, 183 

pressure, 186 

senile, 186 

simple, 184 
Atropine, poisoning by, 29 
Attenuation of bacterial virulence, 113 
Attraction-spheres, 275 
Auditoiy meatus, cholesteatomata in, 436 

mould-fungi in, 670 
Autochthonous pigment, 231 

teratomata. 473 

thrombi, 144 
Auto-intoxications. 75, 78, 80 
Autolysiu, 119 
Autosite, 536 
Awl-tail, 720 

Axis-cylinder, sprouting of, 300 

Bactllace.?:, 580 
Bacilli, 580 

pathogenic, 584 

saproph}'tic, 582 
Bacillus aceticns, 583 

acidi lactici, 582 

aerogenes capsulatus, 603 

amylobacter, 582 

anthracis, 584 

butter, 613, 629 

butyricus, 5^2 

caucasicus, 582 

coli communis, 593 

comma, 660 

cyanogenes, 582 

diphtherise, 597 

fluorescens liquefaciens, 583 

icteroides, 606 



GENERAL INDEX. 



Bacillus iufluenza\. 596 
lepnr, 689 
inallci, 644 

miicosus capsulatus, 596 
cedematis maligui, 602 
pertussis, 597 
pestis, 604 

plilegmones empliysematosa\ 003 
pneumonias of Friedlauder, 595 
prodigiosus, 582 
proteus vulgaris, 583 
pyocyaneus, 583 
smegma, 613 
subtilis, 581 
tetani, 601 

typhi abdominalis, 589 
Bacillus of anthrax, 584 

of blackleg, 656 

of bubonic plague, 604 

of chancroid. 607 

of chicken-cholera, 658 

of contagious pleuropneumonia, 659 

of diphtheria of calves, 659 

of diphtheria of chickens, 659 

of diphtheria of pigeons, 659 

of foot-and-mouth disease, 659 

of glanders and fare}', 644 

of hasmorrhagic septicismia, 658 

of influenza, 596 

of leprosy, 689 

of malignant oedema, 601 

of oz£ena, 596 

of pseudodiphtheria, 600 

of pyelonephritis of cattle, 659 

of rhinoscleroma,-647 

of swine-erysipelas, 657 

of swine-plague, 657 

of symptomatic anthrax, 656 

of syphilis, 681 

of tetanus, 601 

of tuberculosis, 607 

of typhoid fever, 589 

of yellow fever, 606 

of whooping-cough, 597 
Bacteria, 540 

action of, 548 

acid-resisting, 618 

aerobic, 548 

anaBrobic, 548 

association of, 552 

attenuation of, 552 

cultivation of, 558 

degeneration, forms of, 542 

ectogenic, 35 

endogenic, 35 

metastasis of, 551 

movements of, 541 

multiplication, 541 

oligomorphous, 540 

parasitic, 540 

pathogenic, 85, 551 

phosphorescence of, 549 

polymorphous, 541 

products of, 548 

saprophytic, 582 

spores of, 542, 545 

structure of, 541 



Bacteria that cause suppuration, 574 

transmission to foetus of, 551 
Bacteriacese, 580 
Bacteria&mia, 39, 40 
Bacterio-trypsins, 548 
Bacterium, 580 

coli commune, 598 
Bacterium of hjsmorrhagic septicscmia, 658 

lactis at5rogenes, 596 

pneumonice, 595 

typhi, 589 

vulgare, 588 
Balantidium coli, 681 

monatum, 683 
Barbone dei bufali, 659 
Barlow's or Moeller's disease, 158 
Basedow's disease, 88 
Bedbug, or cimex lectularius, 735 
Bedsore, 177 
Beggiatoa, 541 
Benign tumors, 378 
Beri-beri, 19 
Bezoar stones, 226 
Bigerminal tissue-implantation, 480 
Bile-pigment, 244 
Bilharzia hoematobia, 708 
Bilirubin, 244 
Biophores, 62 
Birds, malaria of, 696 

tuberculosis of, 628 
Biting-mite, 784 
Black death, 605 
Black gangrene, 176 
Blackleg, 656 

Bladder, urinary, papillary epithelioma i^f, 
485 

Blastomycetes, 668 

Blebs, haemorrhagic, 157 ^ 
Blennorrhop.a, 335 

of the eye, 577 
Blister, 324, 827 

Blood, antibacterial properties of, 104 

coagulation of, 135 

extravasations of, 156, 235 

parasites of, 682, 692, 696 

protective powers of, 114 
Blood-cells, red, new formation of, 293 

white, new formation of, 292 
Blood-corpuscle cells, 286 
Blood-corpuscles, red and colorless. 294 
Blood-current, slowing of. 138, 139 
Blood-hyalin, 219 
Blood-mole, 497 
Blood -plates, 140 

escape of, from the blood-vessels, 818 

thrombus of, 189 
Blood-poisons, 24 

Blood-serum, bactericidal action, 105 

immuniziuo- power, 113 
Blood-vessels, alterations of walls of, 315 

hvaline degeneration of the walls of, 
"215 

new formation of, 283 
Body-louse, 735 
Bone, in dermoid C3^sts, 483 

necrosis of, 860 

pathological new formation of, 362 



742 



GENERAL INDEX. 



Bone, reproduction of, 288 
Bone-marrrow, reproduction of, 290 
Bones, supernumerary, 525 
Bone-tissue, new formation of, 288 
Bothrioceplialus cordatus, 718 
latus, 716 

latus liguloides, 718 

latus Mansoni, 718 
Botryococcus ascoformans, 580 
Botryomyces, 580 
Botryomycosis, 580 
Botrytis Bassiani, 678 
Botulismus, 18 
Bracliygnatliia, 509 
Brain, concussion of. 16 

development of, 507 

telangiectatic tumor of, 394 
Brain-hernias, 505 
Brain-sand, 223 

Brain-substance in dermoid cysts, 482 
Branchial cysts, 509 

fistulas, 509 
Breast, see also Mammary gland 

adenoma of, 439, 441 
Breasts, supernumerary, 525 

well-developed, in men, 525 
Bronchial calculi, 226 
Bronchitis, purulent, 334 
Bronchopneumonia, 334 
Brood-capsules, 711, 712 
Buboes in plague, 605 
Bubonic plague, 604 
Budding-fungi, 668 
Budding of cells, 277 
Burns, 9 

Butter-bacilli, 613 

Cachexia, 166 

suprarenal, 90 

thyreoprival, 85 

tumor, 379 
Cadaveric alkaloids, 38 

petechias or lividity, 131, 167 
Cadaverin, 38 

Calcaneus, chondroma of, 387 
Calcification, 220 
Calculi, biliary, 227 

bronchial, 226 

dental, 226 

intestinal, 226, 230 . 

prostatic, 227 

salivary, 226 

urinary 228, 230 
Callus, 262. 352 
Calvarium, atrophy of the, 185 
Cancer, see also under Carcinoma, 449 

cells, 451 

cells, hydropic, 190, 467 
cylindrical-celled, 463 
endothelial, 370, 423 
etiology of, 450, 452 
flat-celled. 462 
horny, 463 
medullary, 464 
milk, 451 
plugs, 460, 462 
umbilicatiou, 451 



Cancroids, 458 
Cantharidin, 23 

Carbon- dioxide, influence of, upon devel- 
opment of bacteria, 543 
Carbon-monoxide gas poisoning, 25 
Carcinoma, 449 

acinosum, 464 

adenomatosum, 461, 463 

branchiogenic, 477 

calcification in, 467 

chorionic, 458 

coUoides, 466 

cylindrical -celled, 454, 463 
cylindromatosum, 467 
development of, 449, 453 
different forms of, 462 
" durum, 464 
etiology of, 450, 452 
formation of metastases in, 471 
gelatinosum, 466 
giganto-cellulare, 467 
hyaline degeneration in, 467 
infiltration of, 451, 471 
medullare, 464 
metastasis of, 451, 471 
mucosum, 466 
myxomatosum, 467 
papilliferum, 469 

parasites a possible cause of, 450, 453 

petrifying, 468 

physaliferum, 467 

placental, 458 

retrogi-ade changes in, 451 

scirrhosum, 464 

simplex, 464 

solidum, 461 

squamous-celled, 462 

structure of, 460 

tubular, 460 
Carcinomata, 449 

complete petrification. of» 468 
Cardiac muscle, new development of, 298 
Caro luxurians. 364 

Cartilage, hyaline, reproduction of, 288 

in dermoid cysts, 482 

pigmentation of, 234 

transformation of, into reticular tis- 
sue, 311 
Caseation, 173 

in tubercles, 618 
Castration, effects of, 90 
Catarrh, 324 

chronic, 363 

desquamative, 327 

mucous, 327 

purulent, 327 

serous, 326 
Cattle, actinomycosis of, 649 

tuberculosis of. 628 
Cattle-pest, 116, 579 
Cattle-plague, 116, 580 
Caustics or corrosive agents, 21 
Cavernous tumor, 395 
Cavity-formation in tuberculosis, 621 
Cebocephalia, 506 
Cell-division, 273 
Cell -protoplasm, division of, 275 



GENERAL INDEX. 743 



Cells, hyaline products of, 218 
Central corpuscles, 274 
group, 118 

nervous system, regeneration of, 299, 
302 

Centrosomes, 274 
Cepbalocele, 505 
Cephalotlioracopagus, 535 
Cercaria?, 700 

Cercomonas intestinalis, 681 
Cerebrospinal canal, deficient closure of, 
504 

meningitis, epidemic, 573 
Cerebrum, glioma of, 409 

malformations of, 504 
Cestoda, 705 

Chain-cocci, 540, 559, 561 
Chancre, hard, 632 

soft, 607 
Cheese-poisoning, 18 
Cheesy degeneration, 173 
Cheilo-gnatho-palatoschisis, 508 
Chemicals, as producers of suppuration, 
337 

Chemotaxis, 358, 545 

and chemotropismus, negative and 
positive, 103 
Chemotropismus, 358 
Chicken -cholera, 658 
Chilblains, 10 

Children, predisposition of, 50 
Chills, 95 

Chionyphe Carteri, 655 
Chloasma uterinum. 231 
Chloral hydrate, poisoning by, 29 
Chloroform, poisoning by, 28 
Chloroma, 429 
Chlorosis, Egyptian, 722 
Cholaemia, 80 
Cholera, Asiatic, 660 

protective inoculations against, 664 
Cholera-red, 662 
Choleratoxopeptone, 664 
Cholesteatomata, 436, 475 
Cholesterin, 198 
Cholesterin-calculus, 227 
Cholin, 41 

Chondroblasts, 287, 288 
Choudroitin-sulphuric acid, 209 
Chondroma, 386 
Chondromyxoma, 388 
Chondromy xosarcoma, 387 
Chondrosarcoma, 388 
Chordoma. 388 
Chorio-epithelioma, 458 
Chorionic villi, carcinomatous transforma- 
tion of, 458 
Chromatin, 273 
Chromatophores, 232 
Chromosomes, 274 
Chylangioma, 400 
Chylopericardium, 164 
Chyluria, 164 
Cicatricial tissue, 246 
Cicutoxin, poisoning by, 28 
Cimex lectularius, 735 
Cinnabar, in a tattooed skin, 248 



Circulation, collateral, development of, 
132, 133 

of the blood and of the lymph, dis- 
turbances in, 123 
Cirrhosis of the liver, 365 
Cirrus, 707 

Cirrus-sac of Bothriocephalus latus, 717 

of tsenia solium, 707 
Cirsoid aneurism, 397 

neuroma, 412 
Cladothrix, 541 

asteroides, 655 
Clavus, 262 
Cleft-foot, 519 
Cleft-hand, 519 

Cleft of the abdominal wall, 511 
Clefts, 493 

of the face, median, 508 

of the face, oblique, 508 
Climate, influence of, upon man, 34 
Clitoris, malformations of, 515, 528 
Cloaca, formation of, 515 
Clostridium, 540 

butyricum, 582 
Clothing-louse, 735 
Clots, post-mortem, 134 

lardaceous, 134 
Cloudy swelling, 188 
Clubbed-hand, 521 
Club-foot, congenital, 521 
Clustered cocci, 540 
Coagulation, 134, 317 
Coagulation-necrosis, 172 
Cocaine, poisoning by, 29 
Cocci or coccaceaj, 540, 559 

pathogenic, 560, 561 
Coccidia, 686 

reproduction of, 686. 689 
Coccidium oviforme, 686 

Schubergi, 689 
Coccus mesenterioides, 560 
Coccygeal region, bigerminal teratoma of, 
537 

Colchicine, poisoning by, 29 
Cold, effects of, 10 
abscesses, 621 
Colds, 11 

Collateral circulation, development of, 132, 

134 
Collidin, 41 

Colliquation -necrosis, 174 
Colloid, 203 
cancer, 466 

different uses of the term, 205 
production of, by epithelial cells, 203 
Color-blindness, 55 

Colorless blood -corpuscles, emigration of, 
316 

increase of, relatively to the red, 316 
marginal disposition of, 316 

Coma diabeticum, 82 

Commotio cerebri, 16 

Compensatory hypertrophy, 8, 260 
of the heart-muscle, 260 

Complement, 118, 119 

Compsomyia, 736 

Conceptional infections, 64 



744 GENERAL INDEX. 



Conceptional infections of syphilis, 638 

of tuberculosis, 627 
Concretions, 220 

amyloid, 214 

calcareous, 223, 230 

free, in the body, 226 

uric acid, 230 
Concussions, effects of, 16 
Condyloma acuminatum, 363 

latum, 633 
Congenital predisposition, 47 
Congestion, 129 
Congestive-abscess, 363 
Conglutination, 139 
Conidia-bearers, 672 
Conidia-spores, 669 
Coniine, poisoning by, 29 
Connective tissue, hyaline degeneration 
of, 215 

transformation of, ijito bone, 312 
Connective-tissue structures, regeneration 

of, 286 
Constitutio epidemica, 33 

pestilens, 33 
Constitutional diseases, 52, 81 
Contagium, definition of, 32 

animatum, 34 
Continuous fever, 94 
Convalescence, 94 
Cor villosum, 328 
Cordyceps militaris, 678 
Corn, 262 

Cornification of epithelium, 206 

Cornu cutaneum, 257 

Cornutin, 23 

Corpora amylacea, 214 

Corpulence, 52 

Corrosive agents, 21 

Corynebacterium, 599 

Cows, tuberculous, milk from, 608 

Crab-louse, 735 

Craniopagus, 534 

frontalis, 535 

occipitalis, 535 

parietalis, 535 
Craniorachischisis, 504 
Cranioschisis, 504 

Cranium, faulty development of, 504 

partial agenesia of, 504 
Crayfish pest, 678 
Crenothrix, 541 
Cretinism, 86 

operative, 87 
Crisis, in fevers, 94 
Crossed embolism, 67 
Croupous exudate, 327 

membrane, formation of, on mucous 
surfaces, 328 

pneumonia, 332, 570 
Cruor, 134 

Cryptogenic infections, 41, 568 
Cryptorchismus, 520 
Culicidae, 735 

Culture, methods of bacterial, 553 
Curarine, poisoning by, 30 
Cutaneous horn, 257 
Cuterebra cyaniventris, 736 



Cyanosis, 131 

Cyclencephalia or cycloceplialia, 506 
Cyclopia, 506 

Cylindrical-celled cancer, 454 
Cylindromata, 431 
Cystadeuoma, 442 

multilocular, 442 

papillary, 446 
Cyst-formation, 251 
Cysticercus bo vis, 709 

cellulosas 708 

racemosus, 708 
Cystin, 81 
Cystin-calculi, 230 
Cystocarcinomata, 469 

papilliferum, 469 
Cyst of echinococcus, 711 
Cystofibroma. 447 
Cystomata, 442 

multilocular, 442 

papillary, 442 

simplex, 442 
Cystomyxoma, 447 
Cystosarcoma, 447 
Cysts, branchial, 476. 509 

degeneration, 253 

dermoid, 475 

ectodermal, 475 

entodermal, 475, 476 

mesodermal, 475, 476 

retention, 251 

simple teratoid, 475 

traumatic epithelial, 459 
Cyst- worm, 711 
Cytaster, 278 
Cytoplasm, 219 
Cytoryctes vaccince, 690 

Daltonism, 55 
Darier's disease, 690 
Daughter-cysts of echinococcus. 712 
Daughter-stars, 275 
Daughter-tumors, 375 
Deaf -mutism, 55, 56 
Death, 166 

apparent, 168 
Deciduoma, malignant, 458 
Decomposition, 549 
Decubital necrosis, 171 
Decubitus, 171, 177 
Deer-disease, 658 
Defect, 2, 269 

Defervescence, period of, in fevers, 94 
Degeneration, amyloid, 208 

colloid, 203 

fatty, 190, 194 

granular, 188 

gl^'cogecic, 200 

hyaline, 215 

hydropic, 190 

lardaceous, 208 

mucoid, 201 

parenchymatous, 188 

wax3% 173 
Degenerations, 165. 184 
Deiter's cells, 300 
Demodex, 732, 734 



GENERAL INDEX. 



745 



Dermanyssus avium, 734 
Dermatobia noxialis, 736 
Dermatocoptes, 734 

communis, 734 

cuniculi, 734 
Dermatocysts, 475 

Dermatomycosis dilJusa flexorum, 678 

furfuiacea, 677 
Dermatopliagus, 734 
Dermoid cysts, 475, 481 
Dermoids, 475, 486 
Desmobacteria, 540 
Desmoid tumor, 380 
Destructive placental polyps, 458 
Determinants or determining pieces, 62 
Deuterotoxin, 599 
Development, disturbances of, 488 
Diabetes mellitus, 82 
Diabrosis, 157 
Diapedesis, 157, 316, 319 
Diarrhoea, due to coccidia, 690 
Diastatic ferments, 548 
Diastematomyelia, 502 
Diathesis, lijemorrhagic, 158 

uric acid, 224 
Dicephalus and diprosopus, 534 
Digitalin and digitalein, poisoning by, 30 
Diphtheria, 597, 598 

bacillus of, 597 

blood-serum treatment of, 117 

columbarum, 659 

of calves, 659 

of chickens, 659 

of pigeons, 659 ^ 
Diphtheritic inflammations, 339 
Diphtheritis, 339 
Diplococci, 559, 578, 579 
Diplococcus intracellularis meningitidis, 
572 

lanceolatus, 570 

pneumoniae (Fraenkel.Weichselbaum), 
570 

Diprosopus, 534 
Dipygus, 535 

parasiticus, 538 
Disease, extrinsic causes of, 5 

intrinsic causes of, 47 

latency of, 2 

the symptoms of, 2 
Diseases, cause, origin, and course of, 1 

constitutional, 81 

general, 2, 75 

inheritable, 56 

local, 2 
Dispirem, 278 

Displacement of tissue as a cause of tumor- 
formation, 373, 474 
Dispora caucasica, 582 
Distemper of dogs, 580 
Distoma felineum, 703 

haematobium, 703 

hepaticum, 700 

lanceolatum, 701 

pulmonale, 702 

sibiricum, 703 

spathulatum, 702 

Westermanni, 702 



Distomia, 509 
Disuse atrophy, 187 
Diverticulum, Meckel's, 512 
Dochmius duodenalis, 721 

stenocephalus, 723 

trigonocephalus, 723 
Double monsters, 132, 531 

symmetrical, 533 

unequal, 536 
Dracunculus medinensis, 729 
Drill-bone, 392 
Dropsy, 150 
Druse, 650 

Ductus thoracicus, obstruction of, 164 

occlusion, 152 

rupture of, 164 
Ductus omphalomesaraicus, 512 

thyreoglossus, 476 
Duplications, 523 
Duplicitas anterior, 533 

parallel a, 536 

posterior, 534 
Dura mater, endothelioma of, 422 

osteoma of, 391 

psammoma of, 430 
Dust-diseases, 15, 362 
Dust-particles, entrance of, into the body^ 
67 

metastasis of, 67 
Dwarfs, 52, 179 

formation of, 179 
Dyschromatopsia, 55 
Dyscrasia, 166 

from bacteria, 42 
Dysentery due to amoebae, 681 
Dystopia renis, 520 

Eburneous osteoma, 389 
Ecchondrosis, 387 

physalifera splienooccipitalis, 388 
Ecchymoses, 156 
Ecliinococcus granulosus, 713 

hydatidosus, 713 

multilocularis, 714 

scolecipariens, 713 

veterinorum, 713 
Echinococcus-cyst, 712 
Eclampsia, 69 
Ectodermal cysts, 475 
Ectogenic bacteria, 35 
Ectopia cordis, 512 

interna, 520 

intestini, 512 

testis, 520 

vesicae urinariae, 512 
Eczema, 574 

marginatum, 676 
Egyptian chlorosis, 722 
Elastic fibres, development of, 287 
Electric discharges, powerful eifect of, 13^ 
Elephantiasis, 256 

Grascorum, 639 

liaemangiomatosa, 256 

lipomatosa, 256 

lymphangiectatica, 256 

neuromatosa, 25*6 
Embolism, 66, 148 



746 



GENERAL INDEX. 



Embolism, crossed, 67 

paradoxical, 67 

retrograde, 67 
Embolus, riding, 70 

septic, 148 

straddling, 70 
Embryoid tumors, 484 
Embryoma, 483 

Embryonal tissue, transplantation of, 307 
Embryonic tissue, 286 

development of, in a thrombosed ar- 
tery, 351 
Emigration of white cells, 316 
Emphysema of the skin, 72 
Emphysematous gangrene, 176, 603 
Empusa, varieties of, 678 
Empyenia, 395 
Encephalocele, 505 

Encephalomeningocele nasofrontal is, 505 
Enchondroma, 386 
End-artery, 132, 160 
Endocarditis, 567 
Endochondritis syphilitica, 637 
Endothelioma, 420 

hsemangiotic, 397 

lymphangiotic, 403 
Endothelial cancer, 423 
Endothelium, proliferation of, 284 
Engastrius, 538 
Enostoses, 389 
Enterocysts, 477 
Enterogenous intoxication, 79 
Enteroliths, 226 

Entodermal epithelial cysts, 476 
Entogenic bacteria, 35 
Entozoa, 45 

Enzymes, 100, 105, 548 
Eosinophile cells, 218, 219 
Ephelides, 401 
Epidemic, definition of, 32 
Epidermoids, 437 
Epigastrius, 538 
Epignathus, 538 
Epipygus, 538 
Epispadias, 514 
Epistaxis, 156 

Epithelial cysts, ectodermal, entodermal, 
and mesodermal, 475 

after transplantation, 308 

dermoid, 475, 481 

epidermoid, 475 

traumatic, 459 
Epithelial pearls, 207, 463 
Epithelioid cells. 297, 344, 609 
Epithelioma, 434 

contagiosum, 687 

papillary, 434 
Epithelium, atypical growth of, in carci- 
noma, 449 

hyperplasia of, 280 

metaplasia of, 312 

misplaced, development of a cancer 

from, 458 
pathological cornification of, 206 
protective powers of, 99 
regeneration and hyperplasia of, 280 
transplantation of, 306, 475 



Epizoa, 45 

Ergotism, 23 

Erysipelas, 562 

Erythema multiforme, 567 

Erythrasma, 677 

Erythroblasts, 293 

Erythrocytolysis, 135 

Erythrocytorriiexis, 135 

Erythrocytoschisis, 135 

Ether, poisoning by, 28 

Ethmocephalia, 506 

Ethmoid bone, osteoid sarcoma of, 429 

Eurotium, 671 

malignum, 671 • 
Eustrongylus gigas, 723 
Eventration, 512 
Exencephalus, 505 

Exhaustion due to excessive functional 

activity of an organ, 7 
Exhaustion-theory of immunity, 112 
Exostosis, 389 

cartilaginous, 390 

connective-tissue, 390 
Exstrophia intestini, 512 

vesic£e urinariae, 512 
Extravasate, 156 
Extravasations of blood, 156, 235 
Extremities, defective development of, 
516 

duplication of, 523 
Exudate, cellular, 334 

croupous, 327 

fibrinous, 327 

fibrinopurulent, 336 

hsemorrhagic, 332 

purulent, 335 

serofibrinous, 327 

serous, 326 
Exudates, absorption of, 341 
Eye, regeneration processes in, 303 

Face, malformations of, 508 

•Facial hemiatrophy, 187 

Facies leontina in leprosy, 641 

Facultative anaerobes, 543 

Fallopian tube, dropsy of the, 118 

Farcy, 644 

Fastigium, 94 

Fat-embolism, 69 

Fat-granule cells, 196, 197 

Fats, the, 198 

Fat-tissue, atrophy of, 193 

new-formation, 290 
Fatty degeneration, 194 

deposit, 191 
Favus,'675 
Febris continua, 94 

intermittens, 94 

recurrens, 95 

remittens, 94 

subcontinua, 94 
Feet, abnormal positions of, 516, 521 
Felt-louse, 735 
Femur, absence of, 518 
Fermentation, 549, 550 
Ferments, diastatic and inverting, 548 
Ferret-disease, 658 



GENERAL INDEX. 



Fever, 92 

bactericidal action of, 110 
continuous, 94 
etiology, 96 
intermittent, 94 
malarial, the cause of, 692 
relapsing, 95, 666 
remittent, 94 
stages, 93 

yellow, cause of. 606 
Fibrillated connective tissue, development 

of, 287 
Fibrin, 135 
Fibrin-ferment, 136 
Fibrinopurulent exudates, 331, 336 
Fibrinous deposits, 327 

exudates, 327 
Fibro-adenoma, 440 

conversion of, into a carcinoma, 455 

intracanalicular, 441 

papilliferum, 441 

pericanalicular, 381 
Fibroblasts, 287 
Fibrolipoma, 384 
Fibroma, 380 

intracanaliculare, 441 

multiple, 381, 412 

oedematous, 381 

papillare, 441 

pericanaliculare, 381 
Fibromatosis of the nerves, 412 
Fibromyoma, 406 
Fibro myxoma, 382 
Fibrosarcoma, 418 
Filaria Bancrofti, 164, 730 

liaematica, 730 

medinensis, 729 

papillosa, 730 % 

sanguinis liominis, 164, 729 
Filar mass, 278 
Fingers, dwarfing of, 519 
■ malformations of, 519 
Finkler- Prior spirilla, 664 
First intention, repair by, 346 
Fish-poisoning. 19 
Fission-fungi, 540 

methods of examining, 553 

pathogenic, 551 
Fissura abdominalis, 511 

abdominalis intestinalis, 513 

genitalis, 512 

sterni, 512 

vesicce urinariae, 512 
Fistula colli congenita, 509 
Fistulous tracts, 336 
Flagella, 541 
Flagellates, 681, 683 
Flat foot, 521 
Flea, or pulex irritans, 735 
Flemming's germ-centres, 293 
Flesh-thrombus, 497 
Fleshy moles. 401 

wart, 402 
Flies, biting ((Estridae), 735 

common (Stomoxyidae), 735 

stinging (Muscidae), 736 
Foetal glands, persistence of, 476 



Foetal glands, remains, development of a 

cancer from, 458 
Foetus papyraceus, 532 

syphilitic infection of, by either the 
sperm or the ovum, 638 
Food, effects of lack of, 6 
Foot-and-mouth disease, 580 
Foot, cleft, 519 

Foreign body in inflammation, 353 

in cyst, 253, 858 

in giant-cell, 358 
Formative cells, 287 

stimuli, 270, 271 
Fowls, typhoid of, 658 
Fractures, effects of, 288 
Fragmentation, 276 
Freckles, 232 
Freezing, effects of, 10 

gangrene due to, 176 
Frettchenseuche, 658 
Friedlander's pneumobacillus, 595 
Frog foetus, 504 
Fructification, act of, 61 
Fuchsinophile bodies, 218 
Fungous granulations, 364 
Fungus medullaris, 368 
Furuncle, 574 

Gadinin, 549 

Gall-ducts, adenocystoma of, 443 
Gall-stones. 226, 227 
Ganglion-cells, new-formation of, 299 
Gangrene, 175 

emphysematous, 176, 603 

due to freezing, 176 

due to heat, 176 

infectious, 177 

marasmic, 177 

neuropathic, 177 

pressure, 177 

putrid, 176 

senile, 176 

symmetrical, 177 

toxic, 177 
Gangrenous inflammation, 340 
Gas, irrespirable, 22 
Gas-phlegmon, 603 
Gastropachia pini, 678 
Gastrophilus equi, 736 

liaemorrhoidalis, 736 

pecorum, 736 
Gastroschisis, 511 

Genitals, external, development of, 530 

malformations of, 514 
Germ-centres of Flemming, 293 
Germ-sac, intermediary, 700 

primary, 700 

secondary, 700 
Germ- variation, primary, 60, 489 
Germinal anlage, misplaced, 474 
Giant-cell sarcoma, 418 
Giant-cells, 276, 358 

embolism of, 69 

foreign body, 358 

in tubercles, 610 

multinuclear, 276, 358 
Giant growth, general, 52, 255, 522 



GENERAL INDEX. 



Giant growth, partial, 255, 522 
Giants. 52, 255 
Giraldes, organ of, 529 
Gland -activit}', cessation of, 82 
Glanders, 644 

Glia-cells, new-formation of, 300 
Glioma, 408 
Glycogen, 199 
Glycosuria, 82 

Gnats (Ciilicidre and Tipiilid;r). 735 
Goblet-cells, 201, 447 
Gonococciis, 576 
Gonorrhoea, cause of, 576 
Gout, 52 

Gouty deposits, 224 
Granula, 218 

Granular degeneration, 188 
Granulation tissue, 343 

formation of, 344 
Granulations, chronic, 363 

fungus, 364 
Granulation tumors, infectious. 363 
Granules, hyaline, 206, 218 

nuclear, 273 

the so-called. 218 
Granuloma ta, 364 
Grape-mole, 497 
Gravel, 228 

Greenish coloration in decomposing ca- 
davers, 168, 242 
Grossammen. 700 
Growth, causes of, 270 
Guinea-worm, 729 
Gummata, 634 
Gyn[ecomastia, 525 

H.^:mamceba LErK.EMi.E. 682 
Hsemangio -endothelioma, 425 
Haemangioma, 393 

cavernosum, 395 

hypertrophicum. 397 

simplex, 393 
Hremangiotic endothelioma, 397 
Htemangiosarcomata, 424 
Ha?matemesis, 156 
Haemathidrosis, 156 
Hcematocele, 157 
Haematochvluria, 730 
Hsematoidin, 236 
Hgematoma, 156 
Hffimatometra, 157 
Hnematozoa, 698 
PIcematuria, 156 
H£Emochromatosis, 235 
Ha?mofuscin, 231, 233 
Haemoglobin, 236 
Haemoglobinaemia, 239 
Haemoglobinuria. 239 
Hemolysin, 118 
Haemopericardium, 157 
Haemophilia, 158 

acquired, 158 

congenital, 56, 158 
Haemoptoe or haemoptysis, 156 
Haemorrhage, 156, 236 

diabrosin, 157 

diapedesin, 157 



Haemorrhage, rhexin. 157 
Haemorrhagic septicaemia, 658 
Haemosiderin, 237 
Haemosiderosis, 237 
Haemosporidia, 692 
Haemothorax, 157 
Hairs in dermoid cysts, 475, 481 
Hairy polypi, 479 

tongue, 207 
Halteridium, 696 
Hand, cleft, 519 

malformations of, 516 
Hands, abnormal positions of, 521 
Hanii:ing-drop cultures, 554 
Harelip, 508 
Harvest-mite, 732 
Hay-fever, 49 

Head, malformations of, 504 
Head-louse, 735 

Healing powers of the human body, 108 

serum, 113 
Heart, action of, 123 

disturbed action of, 124 

fibroid area in, 353 

increased action of, 126 
Heart-muscle, compensatory hypertrophy 
of, 260 

hypertrophy of, 126 

pigment of, 233 

rigor mortis of, 168 
Heart poisons, 28 
Heart-polypi, 144 
Heat-exhaustion, 9 
Heat-stroke, 9 

Helleborin, poisoning b}', 30 
Helvellic acid, poisoning by, 26 
Hemiatrophy, cuimeuital, 187 

facial, 187 

infantile, 187 
Hemicrania, 504 
Hepatitis, chronic, 365 
Hereditary pieces or determinates, 62 
Hereditary transmission, atavistic, 58 

collateral, 58 

direct, 57 

pseudo-form of, 65 
Heredity, degenerative, 57 

identical, 57 

transformational, 57 
Hermaphrodism, false, 528 

true, 527 
Hernia basalis, 506 

cerebri, 505 

funiculi umbilicalis. 511 

lateralis, 506 

nasoethmoidalis, 506 

nasofrontalis, 506 

occipitalis, 505 

sphenoorbitalis, 506 

splienomaxillaris, 506 

sphenopharyngea, 506 

syncipitalis, 506 

umbilical, 511 
Herpes tonsurans, 676 
Herpetomonas Lewi.?ii, 683 
Heterakis, 720 

Heterotopous tissue-growths, 474 



GENERAL INDEX. 



74:9 



Histoid tumors, 367 
Hog-cholera, 658 
Holorachiscliisis, 499 
Holoscbisis, 278 
Homo delinqueas, 53 

sapiens, 54 
Hook-worm, 731 
Horn, cutaneous, 257, 435 
Horny warts, 257, 434 
Horse-flies (Tabanidse), 735 
Humerus, osteochondroma of, 388 
Hunterian induration, 632 
Hyalin, connective -tissue, 219 

epithelial, 203, 206 
Hyaline cartilage, reproduction of, 288 
Hyaline degeneration, 215 

of connective tissue, 215, 219 

of connective tissue of heart, 217 

of connective tissue of vessel-wall, 217 
Hyaline exudations, 219 

products of connective-tissue cells, 
218, 219 

thrombi, 219 

tissue-necrosis, 219 
Hydatid mole, 496, 497 
Hydatids, 711 
Hydrencephalocele. 505 
Hydrocele colli congenita. 510 
Hydrocephalus, 507 
Hydrocyanic-acid poisoning, 25 
Hydrogen-sulphide poisoning. 35 
Hydromeningocele, 501 
Hydromyelocele, 501 
Hydropic degeneration, 190 
Hydrops, 150 

adiposus, 154 

chylosus, 154 
Hydrorachis, 499 
Hydrothorax chylosus, 164 
Hygroma colli congenitum, 400 
Hyoscyamine, poisoning by, 29 
Hypersemia, active, 129 

local, 129 

passive, 130 

venous, general, 130 
Hyperkeratosis, 207 
Hypermastia, 525 
Hyperonychia, 257 
Hyperostosis, 363 
Hyperplasia, 255 
Hyperthelia, 525 
Hyperthyreosis, 88 
Hypertrichosis, 257 
Hypertrophy, 255 

compensatory, 261 

due to lessened use, 261 

due to over-work, 8, 260 

due to non-resolution, 261 

due to removal of pressure, 262 

inflammatory, 262 

of a muscle or gland. 8 

of the tissues and organs, 255, 258, 260 
Hyphce, 43 
Hyphomycetes, 667 
Hypochondria. 17 
Hypoderma'bovis, 786 
Hypoplasia, 178 



Hyposarca, 150 
Hypospadias, 514 
Hypostasis, 131 

post-mortem, 131, 167 
Hypostatic congestion, 131 
Hysteria, 17 

Ichthyosis, 256 

congenita, 256, 257 

hystrix, 257 
Ichthyotic warts, 257, 433, 434 
Ichthyotoxin, 19 
Icterus, 244 

neonatorum, 244 
Idiosyncras}^ 49 
Immune-body, 119 
Immune-sera, 119 
Immunity, 47, 99 

acquiring of. 111 

Ehrlich's theory of, 114, 117 
Immunization, active and passive, 114 
Implantation, 305, 308, 480, 486 

bigerminal, 480 

monogerminal, 480 
Inclusio foetalis, 538 
Indolent ulcers, 363 
Induration, Hunterian, 632 
Infarct, anaemic, 160 

embolic, 161 

ha;morrhagic, 161 

healing of, 162, 352 
Infection, 38, 89 

by means of animal parasites, 45 

cryptogenic, 41, 568, 575 

double, 41 

hcematogenous, 41 

intra-uterine, 40, 552 

origin of disease through, 39 

protection against, 99, 101 

secondary, 41, 626 

spread of, by mosquitos, 46, 697, 730 
spread of, from mother to fcetus, 40, 
64, 552 
Infectious diseases, 31 
healing of, 109 
local, 39 

inheritance of, 64 
Infectious foci, metastatic, 39 
Infiltration, 321 

grow^th of tumors by, 375 

purulent, 335 

serous, 326 

small-celled, 334 
Infiltrations of the tissues, 165, 321 
Infiltrative mode of growth of carci- 

nomata, 451 
Inflammation, 314 

catarrhal, 826, 385 

chronic, 360 

clinical significance of the term, 318 
different forms of, 326 
diphtheritic, 339 
fibrinous, 327 
interstitial, 328 
necrotic, 338 
parenchj^matous, 324 
superficial, 324 



150 



GENERAL INDEX. 



Inflammation, suppurative, 335 

termination of, 341 
Influenza-bacillus, 596 
Infusoria, 681 

Inheritance of pathological peculiarities, 
56 

Initial sclerosis, 632 
Injection of sterilized cultures, 113 
Innervation, disturbances of, 16, 17, 77 
Inoculation, 111 

Inoculation of attenuated specific disease- 
germs, 113 
Insanity, inherited, 53 
Insecta, 735 
Insects, 46, 735 
Insolation, 9 

Insusceptibility to poisons, 100 
Interfilar mass, 278 
Intermediary body, 119 
Intermittent fever, 94 
Internal secretion, 82 
Interstitial inflammation, 323 
Intestinal intoxications, 38 

mucous membrane, adenoma like pro- 
jection of, 476 
Intestine, abnormal positions of, 511, 520 

tubular adenoma of, 438 
Intoxication, origin of diseases through, 

18, 78 
Invasion-disease, 45 
Inversio intestini, 512 

vesicae urinariae, 512 
lodothyriii, 87 
Iron, assimilation of, 242 

deposit, 240 

insufficiency of, 7 

reaction, 237 
Iron -free pigments, 236, 242 
Irradiation, 13 
Ischiemia. localized, 132 
Ischiopagus, 534 
Isolysin, 119 

Isthmus, the, of aorm, 127 
Itch-mite, 731 
Ixodes ricinus, 732 

Janiceps, 535 
Janus-head, 535 

Jarrings of the uterus as a cause of mal- 
formations of the embryo, 489 
Jaundice, 244 

Jaw, upper, actinomycosis of, 652 
giant -cell sarcoma of, 419 
lower, absence of, 509 

Kakerlaken, 250 
Kakke, 19 
Karyokinesis, 273 
Karyo lysis, 169 
Karyomitosis, 273 
Karyorrhexis. 169 
Kedani disease, 734 
Kephir, 582 
Kephir-ferment, 582 
Keloid, 382 
Keratin, 206 
Keratohvalin, 206 



Keratosis follicularis, 690 

Kidney, amyloid degeneration of, 212 

arteriosclerotic atrophy of the, 186 

cloudy swelling of, 189 

compensatory hypertrophy of, 282, 
642 

contracted, 364, 365 

cystoma of, 444 

deposits of fibrin in the, 332 

senile atrophy of, 186 

streptococcus infection of, 568 

tubular adenoma of, 440 
Kinetoses, 17 
Kribbelkrankheit, 23 
Krumelzellen, 354 
Krystallwulst, 303 

Labia major a and minora, defective de- 
velopment of, 515 
Labium leporinum, 508 
Lardaceous degeneration, 208 

spleen, 208 
Larynx, papillary epithelioma of, 435 

syphilitic ulceration of the, 636 
Latency of disease, 2 
Lead-poisoning, 23 
Lead, deposit of, 249 
Leiomyoma, 404 
Lens, regeneration of, 303 
Lentigines, 232, 401 
Leontiasis ossea, 258, 523 

leprosa, 641 
Lepra (or leprosy). 639 

anaesthetica, 642, 643 

maculosa, 642 

mutilans, 642, 643 

nervorum, 642 

nodosa, 642 

tuberosa sive tuberculosa, 642 

ulcerosa, 642 
Lepros3% 639 

white, of the Jews, 251 
Leptothrix, 540 
Leptus autumnalis, 732, 734 
Leucoblasts, 294 

Leucocytes, 106, 110, 334. 335. 344, 356 

emigration of, 316. 325, 353 

new -formation of, 292 

varieties of, 294 
Leucoderma, 250 
Leuconostoc mesenterioides, 560 
Leucopathia acquisita, 250 

congenita, 250 
Leucotrichia, 250 
Leukaemia, 682 
Leydenia gemmipara, 683 . 
Lice, 735 

Life-trophoblasts or biophores. 62 
Light, effects of, 13 

influence of. upon development of 
bacteria, 543 
Lightning figures, 14 
Lightning- stroke, 13 
Linguatulidae, 731 
Lip, carcinoma of, 454 

malformations of, 508 
Lipochrome, 231, 233 



GENERAL INDEX. 



751 



Lipofibroma, 384 
Lipoma, 384 
Lipomatosis, 52, 191 
Lipomyxoma, 384 
Liquefaction-necrosis, 174 
Lithocelyphopaedion, 498 
Lithocelyphos, 498 
Lithopaedion, 498 
Liver, abscess of, 681 

amyloid degeneration of, 209, 211 

angioma cavernosum of, 395 

chronic inflammation of, 365 

cirrhosis of, 365 

coccidia, disease of, 686 

corset, 187 

cystoma of, 443, 444 

foamy, 603 

gumma of, 635 

multilocular adenocystoma of, 444 

Liver-fluke, 700 

Livores, 131, 167 

Lucilia macellaria, 736 

Lungs, actinomycosis of the, 651 
fibrinous exudates in the, 332 
induration of, 362 
mould-fungi in the, 671 
red hepatization of the, 332 
syphilitic disease of the, 637 
tuberculosis of the, 616, 619, 620, 622, 
623 

Lupus of the skin, 617 
Lustgarten's bacillus of syphilis, 631 
Luxations, congenital, 521 
Lymph, antibacterial properties of, 104 

formation of, 151 

hindrance of flow of, 152 
Lymphadenoid tissue, reproduction of, 

290, 291 
Lymphangioma, 399 

cavernosum. 400 

cystoides, 399 

hypertrophicum, 400 

simplex, 399 
Lymphangiosarcoma, 420 
Lymphangoitis, 40 
Lymph-fistula, 164 

Lymph-glands, action of, as filters, 104 
Lymphorrhagia, 163 
Lymphosarcoma, 416 
Lysis, in fever, 94 

Lysogenous substance of Frankel, 109 

Macrocheilia, 400 
Macrogamete, 689, 698 
Macroglossia, 400 
Macrostomia, 509 

Madura disease or Madura foot, 655 
Maidismus, 38 
Malanders, 734 
Malaria, 692 

forms of, 692 

in animals, 696 

Plasmodia of, 692 

the cause of, 692 
Malformations, 488 

congenital, 488 
Maliasnius, 644 



Malignant adema, 602 
tumors. 379 

Mallein, 646 

Malleus, 644 

Mai perforaut, 177 

Mammary gland, adenoma of, 439 
carcinoma of, 462, 464 
endothelioma of, 423 
intracanalicular fibroma of, 441 
mucous carcinoma of, 465, 466 
papillary cystocarcinoma of, 327, 
469 

papillary cystoma of, 448 
tubular adenoma of, 439, 457 

Marasmic thrombi, 144 

Marasmus, 6, 166 

Margarin crystals, 199 

Mast-cells, 218 

Mastoid antrum, cholesteatomata in, 486 
Measles of taeniae, 708 
Meat-poisoning, 18, 38 
Meckel's diverticulum, 512 
Mediastinal dermoids, 476 
Medullary cancer, 464 
Megastoma entericum_, 682 

intestinale, 682 
Melaena neonatorum, 159 
Melanin, 233 
Melanomata, 400 
Melanosarcomata, 428 
Melanosis of internal organs, 234 
Melasma suprarenale, 89 
Membrane, pyogenetic, 353 
Meningitis, epidemic cerebrospinal, 573 
Meningocele, 500, 505 
Meningococcus, 572 
Meningo encephalitis syphilitica, 634 
Meningo-encephalocele, 505 
Menorrhagia, 156 
Merismopedia, 540, 541, 559 
Merorachischisis, 499 
Merozoites, 689, 698 
Mesodermal epithelial cysts, 476 
Metabolism, bacterial, 548 
Metaglobulin, 141 
Metakinesis, 274, 278 
Metamorphosis, viscous, 139 
Metaplasia, epithelial, 312, 578 

of the tissues, 310 
Metastasis, 66 

direct, 67 

formation of, in carcinomata, 451 

haematogenous, 66 

in tuberculosis, 623 

lymphogenous, 66 

of pigment, 72 

paracloxical, 67 

retrograde, 67 
Metastatic daughter-tumors, 70, 875 

infectious foci, 71 

inflammations, 66 
Methaemoglobin, 239 

the formation of, 26 
Methaemoglobin uria, 239 
Methyl guanidin, 38 
Metrorrhagia, 156 
Miasm, definition of, 32 



T52 



GENERAL INDEX. 



Miasmatic -contagious disease, definition 
of, 32 

Miasms and contagious, boundary-line be- 
tween, 35 
IMicrenceplialon, 53 
Micrenceplialus, 180, 505 
Microbacteria,. 540 
Microbracliius, 516 
Microgamete, 689, 698 
Microceplialus, 180, 505 
Micrococci, 540, 559 
Micrococcus ascoformans, 580 

aurantiacus, 560 

botryogenes, 580 

cyaneus, 560 

gonorrhoeae, 576 

liaematodes, 560 

in meningitis, 572 

in mycofibroma, 580 

in mycosis of parrots, 580 

in pseudotuberculosis of guinea-pigs, 
580 

luteus, 560 

of foot-and-mouth disease, 580 
of hfemoglobinuria of cattle, 580 
of lung-disease of horses, 579 
pathogenic, 560, 561 
pyogenes, 573 
pyogenes of rinderpest, 579 
tetragenus, 560 

tetragenus of udder-disease, 580 

ureae, 560 

violaceus, 560 

viscosus, 560 

xantogenicus, 607 
Microgametocyte, 689, 698 
Microgyria, 180 
Micromelus, 516 
Micromyelia, 53 
Micropus, 516 
Microsomes, 278 
Microsomia, 496 
Microsporon furfur, 677 

minutissimum, 677 
Microstomia, 509 
Miescher, sacs of, 688 
Miliary tubercles, 611, 616, 624 

tuberculosis, haematogeuous. 625 
Milk from tuberculous cows, 608 
Mineral poisons, 18 
Miracidium, 700 
Missed labor, 498 
Mites, 731, 734 
Mitome, 278 
Mitosis, 273 
Mole, 400 

hairy, 400 

hydatid, 497 

pigmented, 400 
Moller's or Barlow's disease, 158 
Molluscum bodies, 687 
Monas lens, 682 
Monilia Candida, 672 
Monobrachius, 516 

Monogerminal tissue-implantation, 480 
Monomorphous bacteria, 540 
Monopus, 516 



Monsters, 488 

double, 494, 531 

triple, 531 
Morbus Addisonii, 89, 231 

maculosus Werlhofii, 158 
Morgagni, hydatid of, 529 
Morphine, poisoning by, 29 
Morphoea nigra et alba, 642 
Mosquitos, agency of, in spreading certain 

diseases, 46, 697, 730 
Mother-star, 274, 277 
Mouldering, 550 
Mould-fungi, 668, 669 
Mouth, development of, 510 

malformations of, 509 
Mucins, the, 202 
Mucor corymbifer, 671 

pusillus, 673 

ramosus, 673 

rhizopodiformis, 673 
Mucorini, disease-producing, 43 
Mucous degeneration, 201 

membranes, carcinoma of, 454 

membranes, papillary epitheliomata 
of, 435 

tissue, reproduction of, 291 
Muguet, 670 
Mailer's duct, 529 

Multiple fibromata of the skin, 54, 412 

Mummification, 176 

Muscardine in silkworms, 678 

Muscarin, poisoning by, 30 

Muscidae, 738 

Muscle, atrophy of, 185 

heart, hypertrophy of, 266 
heart, new-formation of, 298 
in dermoid cysts, 482 
non-striated, hypertrophy of, 298 
non-striated new-formation of, 298 
striated, hj^pertroph}^ of, 260 
striated, new-formation of, 296 
waxy degeneration of, 173 

Muscle-trichina, 727 

Muscles, cadaveric stiffening of, 168 
supernumerary, 525 

Muscular system, pathological changes in 
the, 53 

Mussel poisoning, 19 

Mycelium, 669 

Mycetoma, 655 

Mycobacterium tuberculosis, 618 
Mycoderma albicans, 672 
Mycodesmoid, 580 
Mycofibroma, 580 
Mycoprotein, 541 
Mycosis of alimentary tract, 670 

of respiratory tract, 670, 673 

of skin, 675 

versicolor, 677 
Mycosozin, 105 
Myelocele, 501 
Myeloc3''stocele, 501 
Mj^elocj^stomeningocele, 502 
Myelocysts, 477 
Myelomeningocele, 500 
Myiasis, 736 
Myofibroma, 406 



GENERAL INDEX. 



T53 



Myolipoma inside the vertebral canal, 

474 
Myoma, 404 

Isevocellulare, 404 

striocellulare, 406 
Myosarcoma, 407 
Myositis ossificans, 53, 392 
Myxoangiosarcoma, 431 
Myxoedema, 86 
Myxofibroma, 383 
Myxolipoma, 383 
Myxoma, 382 
Myxosarcoma, 382 

N^VUS FLAMMEUS, 394 

lymphaticus, 400 
pigmentosns, 400 
pilosus, 400 
prorcinens, 395, 400 
spilus, 400 
vasculosus, 395 
verrucosus, 395, 400 
vinosus, 394 
Nanosomia, 496 

Nasal muscous membrane, lymphosar- 
coma of, 416 
Navel stone, 227 
Neck, malformations of, 508 
Necrobiosis. 171, 173 
Necrosis, 169 

anaemic, 170 

cheesy, 173 

coagulation, 172 

colliquation, 173 

decubital, 177 

direct, 171 

indirect, 171 

marasmic, 171 

mummifying, 176 

neuropathic, 170, 177 

senile, 176 

thermal, 176 
Nemathelminthes, 718 
Nematoda, 718 

toxic, 177 
Nematodium ovis pulmonalis, 723 
Nerve- and heart-poisons, 28 
Nerve elements, new formation of, 299 
Nerve-fibres, peripheral, new formation 
of, 303 

peripheral, pathological changes in, 
54 

Nerves, fibromata of, 412 

fibromatosis of, 412 

leprosy of, 642 

regeneration of, 301 
Nervous system, central, pathological 

changes in the, 53 
Neurasthenia, 17 
Neuridin, 38, 549 
Neurin, 38, 549 
Neuroepithelioma, 409 
Neurofibroma, 411 

Neuroglia, hypertrophic growth of, 300 
regenerative growth of, 300 

Neuroglioma ganglionare, 409 

gliomatosum microcysticum, 410 
40 



Neuroma, 411 

amputation, 302, 411 
amyelinicum, 413 
cirsoid, 412 

ganglion cellulare verum, 413 

myelinicum, 412 

plexiforme, 412 

verum, 412 
Neuropathic atrophy, 187 

gangrene, 177 

necrosis, 170 
Neuroses, traumatic, 17 
Neurotization, 302 
Nicotine, poisoning by, 29 
Nitrate- of -silver poisoning, 23 
Nitrobacteria, 549 

Nitrogenous nourishment, importance of, 6 
Nitrous oxide, poisoning by, 28 
Nodes, gouty, 225 
Normal serum, 117 
Nuclear contents, 273 

framework. 273, 278 

granules, 273, 278 
Nuclear division, asymmetrical, 275 

atypical, 275 

direct, 273, 276 

indirect, 273 

plueri polar, 275 

segments, 274 

spindle, 274 
Nuclein, 273 
Nucleinic acid, 106 
Nucleus, composition of the, 273 
Nutrition, retrograde disturbances of, 165 

Obesity, 52, 191 
Obligate anaerobes, 543 
Obturating thrombus, 144 
Ochronosis of cartilage, 234 
Odontoma, 389 
(Edema and dropsy, 150 

cachectic, 153 

collateral, 153 

due to obstruction of thoracic duct, 
152 

ex vacuo, 153 
hydrEEmic, 153 
inflammatory, 153 
malignant, 602 
purulent, 386 
stagnation, 152 
(Esophagus, growth of apnthse upon the, 
670 

(Estridse, 736 
(Estrus bovis, 736 

ovis, 736 
Oi'dium albicans, 672 

subtile cutis, 673 
Olein, 198 

Oligomorphous bacteria, 540 
Omentum, tuberculosis of, 626 
Omphalocele, 511 
Omphalomesenteric cyst, 513 

duct, 512 
Oncosphsera, 717 
Onychogryphosis, 257 
Onychomycosis favosa, 676 



GENERAL INDEX. 



lit ' 

Onychomycosis trichophytina, 676 
Oocyst, 686, 689, 698 
Ookinete, 697, 698 

Opium and morphine, poisoning by, 29 
Organs, weight of, 259 

volume of, 259 
Osteoarthropathie hypertrophianle, 263 
Osteoblasts, 290 
Osteochondroma, 388, 391 
Osteofibroma, 391 
Osteoid sarcoma, 430 

of ethmoid, 429 

trabeculce, 430 
Osteoma, 389 

dental, 389 

disconnected, 389 

durum seu eburneum, 389 

heteroplastic, 389 

medullare, 389 

parosteal, 389 

spongiosum, 389 
Osteomyelitis, 574 
Osteophyte, 389 
Osteoporosis, 183, 184 
Osteosarcoma, 419 
Ovary, adenocystoma of, 445 

dermoid cysts of, 481 

multilocular adenocystoma of, 443 

papillary cystadenoma of, 445, 447 

papillary cystocarcinoma of, 470 

cj^stoma of, 446 

teratomata of, 483 
Over-exertion, 7 
Over-heating, 9 

Overwork, hypertrophy from, 260 

Oxidation, intra-organic, 91 

Oxygen, effects of a diminution in the 

supply of, 5 
influence of, upon development of 

bacteria, 543 
Oxyuris vermicularis, 720 

Pachyakria, 263 

Packet-shaped cocci, 540, 560 

Paget's disease, 690 

Palate, malformations of, 508 

Palmitin, 198 

Pancreas, C3"st of the, 252 

diabetes after extirpation of, 83 
Papillary adenomata, 440 

conversion of, into a carcinoma, 456 

cystomata, 446 

epitheliomata, 434, 436 
Papilloma, 380 
Paracholia 245 

nervous, 245 
Paradoxical embolism, 67 
Parakeratosis, 207 
Paralysins, 110 
Paramtecium coli, 681 
Paramitome, 278 
Paramucin, 203 
Paraplasm, 278 

Parasite (in the case of twins), 536 
Parasites, 31 
animal, 679 

formation of cysts by, 253 



Parasites, metastasis of, 71 
Parasitic diseases, 33 

infection, 33 
Parasitism, origin of disease through, 31, 
33 

Parenchymatous cells, embolism of, 69 
Parenchymatous degeneration, 188 

inflammation, 324 
Parietal thrombus, 144 
Parotid gland, angiosarcoma of, 426 

chondrofibroma of, 426 

chondromyxosarcoma of, 387 

myxoangiosarcoma of, 431 
Parosteal osteomata, 389 
Parrots, mycosis of, 580 
Pathology and pathological anatomy, the, 1 

clinical, 3 

general, definition of, 1 

problems of, 1 
Pearl disease, 628 

tumors, 436 
Pearls, epithelial, 207, 436, 463 
Pediculus capitis, 735 

pubis, 735 

vestimentorum, 735 
Pellagra, 19, 38 
Penis, duplication of, 525 

stunting of, 514 
Pentastoma, 731 

denticulatum, 733 

tsenioides, 733 
Peptotoxin, 549 
Peribronchitis, 334 

Peripheral nerves, pathological changes 

in, 54 
Perithecia, 673 
Perithelioma, 426 

Peritoneum, cystic lymphangioma of, 400 

Peritrichous flagella, 602 

Perlsucht, 628 

Pernicious malaria, 694 

Perniones, 10 

Perobrachius, 516 

Perochirus, 519 

Perodactylism, 519 

Peromelus, 516 

Peropus, 516, 519 

Perturbatio critica, 94 

Pes calcaneus, 521 

equinovarus, 521 

valgus, 521 
Pest, 604 

bacillus, 604 
Pestilence, definition of, 32 
Petechise, 156 
Petrifaction, 220 

in carcinomata, 468 
Petrifving sarcoma, 430 
Phagocytes, 99, 103. 356 
Phagocytosis, 99, 103, 356 
Phallin, poisoning by, 26 
Phimosis, hypertrophic, 515 
Phleboliths, 146, 227 
Phlegmon, 336 

wooden, 568 
Phloridzin diabetes, 84 
Phocomelus, 516 



GENERAL INDEX. 



755 



Phosphorescent phenomena, 549 

Physalides, 467 

Physiology, pathological, 1 

Pia mater, cholesteatomata of the, 437 

Pigeon-diphtheria, 659 

Pigment, autochthonous, 231 

extrinsic, 248 

hsematogenous, 235 

metastasis of, 73 

pathological absence of, 250 

pathological formation of, 231 
Pigment-atrophy, 183 
Pigment-carrying cells, 236, 237 
Pigment-granule spheres, 857 
Pigmented mole, 400 

warts, 400 
Piroplasma bigeminum, 696 
Pithead tapeworm, 716 
Pityriasis, 675 

versicolor, 677 
Placental cells, embolism of, 69 

infections, intra-uterine, 552 

polyp, malignant, 458 

villi, carcinomatous transformation, 
458 

Placentoma, 458 
Plague, bubonic, 604 
Plasma-cells, 354 
Plasmodium malarige, 692 

praecox, 692 

vivax, 692 
Plasmolysis, 135 
Plasmorrhexis, 135 
Plasmoscliisis, 135, 169 
Plasmosomes, 278 
Plate-cultures, 553 
Platyhelminthes, 700 
Plerocercoid, 718 
Plethora, 126 

Pleura, endothelioma of. 422 
Pleuritis, fibrinous, 331 
Pleuropneumpnia, contagious, of cattle, 
579 

Plexiform neuroma, 413 

Plugs, epithelial, in cancer of the skin, 460 

Pluripolar division, 275 

Pneumococcus, 570 

Pneumonia, croupous, 332, 570, 595 

infectious, of cattle, 659 

of horses, 579 
Pointed condylomata, 362 
Poisoning, definition of, 18 
Poisons, classification of, 21 

dillerent varieties of, 21 
Poison-theory, of immunity, 112 
Polar area, 278 

corpuscles, 274, 278 

furrow, 500 
Poliosis, 250 
Polydactylism, 523 
Polymastia, 525 
Polymelos, 537 
Polymitus, 695 

Polymorphism of cancer-cells, 451 
Polymorphous bacteria, 541 
Polypi, hairy, 479 
valvular, 145 



Polythelia, 525 
Polyuria, 56, 82 

Post-mortem hypostasis, 131, 167 
Potassium chlorate poisoning, 26 
Predisposition, acquired, 48 

congenital, 52 

local, 48 

temporary, 48 
Prepuce, absence of, 515 

hypertrophy of, 515 

shortness of, 515 
Pressure atrophy, 186 
Pressure, continuous, effects of, 15, 186 
Proglottides, 705 
Proliferation, phenomena of, 343 
Proscolex, 715 
Prosoposchisis, 508 
Prosopothoracopagus, 536 
Prostatic concretions, 205 

calculi, 227 
Protective mechanisms, natural, 99 
Proteosoma, 696 
Proteus vulgaris, 583 
Prothrombin, 136 
Protophyte, 540 
Protoplasm, 275 
Prototoxin, 599 
Protozoa, parasitic, 680 
Psammomata, 430 
Pseudalius ovis pulmonalis, 723 
Pseudo-actinomj^cosis, 655 
Pseudodiphtheria bacilli, 600 
Pseudohermaphrodismus, 528 
Pseudomelanosis, 238 
Pseudomucin, 202 
Pseudotuberculosis, 580, 628 

aspergillina, 629, 673 

cladotrichica, 629, 655 

due to animal parasites, 629 

due to bacteria, 629 

due to foreign bodies, 628 

due to hyphomycetes, 629 

vermian, 629 
Psorospermose folliculaire vegetante, 690 
Psychoneurosis, 17 
Ptomains, 88, 41, 548 

toxic, 38, 549 
Pulex irritans, 785 

penetrans, or sand flea, 735 
Pulmonary circulation, increase of resist- 
ance in, 127 
Pulse, acceleration of, 125 

venous, 125 
Puriform softening, 146 
Purpura, 158 

haemorrliagica, 158 

rlieumatica, 158 

simplex, 158 
Pus, 835 

inspissated, calcification of, 853 
Pus-cocci, 574 
Pus-corpuscles, 385 
Pustule, 385 
Putrefaction, 88, 41, 549 

alkaloids, 38, 41 

zymoids, 41 
Putrescin, 88, 549 



756 



GENERAL INDEX. 



Putrid gangrene, 176 
Pyaemia, 40, 566, 575 
Pyelonephritis of cattle, 659 
Pygopagus, 533 
Pyknosis, 169 
Pyoseptlisemia, 566 
Pyosepticaemia, 40, 566, 575 

Quinine, poisoning by, 29 

Rabies, protective inoculations against, 
116 

Rabbit septicaemia, 658 
Race, predisposition of, 51 
Rachicele, 500 
Rachipagus, 536 
Rachischisis, partial, 499 

total, 499 
Rag-sorters' disease, 587 
Rainey's bodies, 688 
Ray-figures, 275 
Ray -fungus, 649 
Rays, 275 

Recurrent fever, 95 
Receptaculum scolicis, 708 
Rectum, cancer of, 461 
Rediae, or secondary germ-sacs, 700 
Reduplications, 523, 533 
Regeneration, 265 
causes, 266 

of degenerated tissue, 342 

partial, 267 
Regenerative capacity of tissues, 269 
Relapsing fever, 95. 666 
Remittent fever, 94 

Repair by first and by second intention, 
346 

Respiratory apparatus, aspergillus my- 
coses of, 673 

Resting-cells, 273 

Restitutio ad integrum, 267 

Retention cyst, 251 

Retina, glioma of, 409 

Retrograde changes, 451 

Rhabditis stercoralis, 725 

Rhabdomyoma, 406 

Rhexis, 157 

Rhinoscleroma, 647 

Rhizopoda, 680 

Ribs, supernumerary, 58, 525 

Rice-water intestinal discharges in cholera, 
662 

Ricin, 27 

immunity to, 117 
poisoning by, 27 

Rider's bone, 392 

Rigor mortis, 168 

Rinderpest, immunization, 116 

Ringworm, 676 

Roseola syphilitica, 633 

Round-cell sarcoma, 416, 417 

Roundworms, 718 

Rudimentary twin, 480, 532, 536 

Russel's bodies, 206, 218 

Saccharomyces ellipsoideus, 669 
lithogenes, 673 



Saccharomyces neoformans, 673 
Saccharomycetes, 673, 679 

disease-producing, 669, 673 
Sacs of Miescher, 688 
Sago -spleen, 208 
Salts, caustic, 22 

Sand flea, or pulex penetrans, 735 

tumors, 430 
Santonin, poisoning by, 29 
Saprophytes, 543 
Saprophytic bacilli, 582 

cocci, 560 
Sarcina lutea, 560 

ventriculi, 560 
Sarcinae, 560 
Sarcoma, 414 

adeno-, 468 

angio-, 426 

alveolar, 420 

cysto-, 447 

etiology of, 415 

fibro-, 415, 416, 418 

giant-cell, 418 

haemangio-, 424, 426 

large round-celled, 417 

lymphadenoides, 416 

lymphangio-, 420 

lympho-, 416 

medullary, 415 

melano-, 428 

myo-, 419 

myxo-, 419 

organoid, 420 

osteo-, 419 

osteoid, 430 
' petrifying, 430 

phyllodes, 447 

plexiforme, 426 

polymorphous-celled, 417, 418 

simple, 416 

small, round-celled, 416 

spindle-celled, 417 

telangiectatic, 415 

tubular, 420 
Sarcocarcinoma, 468 
Sarcophilia Wohlfarti, 736 
Sarcoplasm, 297 
Sarcoptes hominis, 731 

minor, 734 

squamiferus. 734 
Sarcosporidia, 688, 690 
Sausage-poisoning, 18, 38 
Scabies, 732 
Scald-head, 675 
Scall, 675 
Scar-tissue, 267 
Schistoprosopia, 508 
Schizogony, 682, 686, 689, 698 
Schizomy.cetes, 540 
Schizont, 689, 697, 698 
Scirrhus, 464 

Sclera, regeneration of, 303 
Scleroma respiratorium, 647 
Sclerosis, 216 

initial, 632 

of nerve-tissue, 300 
Scolex, 705 



GENERAL INDEX. 



757 



Scrofula, 637 

Scrotum, malformations of, 515 
Scurvy, 158 
Scutula of favus, 675 
Sea-sickness, 17 

Sebaceous glands in dermoid cysts, 482 
Secale cornutum, 23 
Second intention, repair by, 346 
Secondary infection, 41, 626 
Secretion, internal, 82 
Segmentation, direct, 273 

indirect, 273 
Segmented skein, 274, 277 
Semilunar ganglia, pathological changes 

in, 90 
Sepsin, 41 
Sepsis, 40 

Septicaemia, 40, 566, 575 

hsemorrhagic, 658 
Septicopysemia, 40, 566, 575 
Sequestration of necrosed tissue, 171, 341, 
360 

Serpiginous ulcers, 363 
Serum, healing, 113 

protective, 113 
Sex, predisposition of, 51 
Sexual glands, teratoid tumors of, 481, 486 

removal of, 90 
Sexual organs, internal, development of, 
529 

Shock, erethistic and torpid, 16 

Sickness, causes of, 5 

Side-chains, 118 

Siderosis, haematogenous, 240 

Silver, deposit of, 23, 249 

Sirenomelia, 517 

Situs inversus, 520 

Skein-like structure of the nucleus, 274, 
■ 277 

Skeleton, pathological changes in the, 53 
Skin, absence of pigment of, 250 

cancer of, 453 

emphysema of, 72 

healing of wounds of, 346 

leprous nodule of the, 640 

lupus of the, 617 

melanotic alveolar sarcoma of, 429 
multiple fibromata of the, 54 
papillary epithelioma of, 433 
pathological alterations of, 55 
pigmentation of, 89, 231 

Skin- transplantation, 306 

Skull-cap, angioma cavernosum of, 397 

Slumber-cells, 325 

Smallpox, pustule, 334 
parasites of, 690 

Smear cultures, 553 

Smegma bacillus, 613 

Snake poison, 22 

immunization, 117 

Soft chancre, 607 

Special sense, organs of, new-formation of 

the tissues of, 303 
Specificity of the tissues, 266 
Spermin, ^91 
Sphacelinic acid, 23 
Sphacelus, 176 



Sphaerobacteria, 540 

Spheres, fatty granule, 196, 357 

pigmented granule, 357 
Spider cells, 300 
Spina bifida. 498 

anterior, 500 

cystica, 499 

lumbosacralis, 500 

occulta, 500 

posterior, 500 
Spinal column, pressure atrophy of the, 
187 

cord, development of, 507 
Spindle-celled sarcoma, 417 
Spindle-figure, 277 
Spindle, nuclear, 274, 278 
Spirilla, or spirillaceae, or spirobacteria, 
659 

Spirillum cholerse Asiaticse, 660 

of Finkler and Prior, 664, 665 

rugula, 659 

serpens, 659 

sputigenum, 665 

tenue, 660 

tyrogenum, 665 

undula, 660 

volutans, 660 
Spirobacteria, 659 
Spirochaete, 540, 659 

buccalis, 660 

denticola, 660 

Obermeieri, 666 

plicatilis, 660 

varieties of, 660 
Spleen, amyloid degeneration of, 208 

changes in, in relapsing fever, 666 

tissue, reproduction of, 290 
Sporangia, 671 
Spore-formation, 542 
Spores, 36, 542, 669, 698 
Sporoblasts, 688, 698 
Sporocyst, 688, 689 
Sporogenous granules, 545 
Sporogony, 686, 689, 698 
Sporozoa, 686 
Sporozoites, 686 
Stab-cultures, 533 
Stadium amphiboles, 94 

decrementi, 94 

incrementi, 94 
Staggers, cause of the, 710 
Staphylococci, 540, 573 
Staphylococcus pyogenes albus, 576 

pyogenes aureus, 573 

pyogenes citreus, 576 
Stars, 274, 275, 277 
Starvation, 6 
Stasis of the blood, 149 
Stearin, 198 
Sterigmata, 672 

Sterilized cultures, injection of, 113 
Sternopagus, 536 
Stigmatization, 159 
Stomach, carcinoma of, 456 
Stonioxyidae, 735 
Stones (concretions), 226 
Stone-cutter's lung, 362 



758 



GENERAL INDEX. 



Straddling emboli, 70 
Strangles of horses, 579 
Streptococci, 540, 561 
Streptococcus articuloriim, 569 

brevis, 569 

erysipelatis, 569 

lanceolatus, 570 

longus, 569 

meningitidis, 572 

puerperalis, 569 

pyogenes, 561 

scarlatiuosus, 569 
Streptotiirix madurge, 655 
Strongylides, 728 
Strongylus armatus, 723 

broncbialis, 723 

capillaris, 723 

commutatus, 723 

duodenalis, 721 

filaria, 723 

longevaginatus, 723 

micrurus, 723 

paradoxus, 723 

pusillus, 723 

rufescens, 723 

syngamus, 723 

tetracanthus, 723 

trachealis, 723 
Strychnine, poisoning by. 29 
Substance, fibrinogenic, 141 
Substance, lysogenic, 109 
Substance, zj^moplastic. 141 
Sucking-mite, 734 
Sucking-worms, 700 
Suffocation, 5 
Suffusion, 156 
Suggillations; 156 
Sulphur-metha^moglobin, 26 
Sunstroke, 9 

Supernumerary organs, 53, 523 
Suppuration, cause of, 336 
Suprarenal cachexia, 90 

capsules, altered function of, 89 
Suprarenin, 90 
Surra, 684 

Susceptibility to infections at different 
ages, 50 

Sweat-glands in dermoid cysts, 482 
Swine-erysipelas, 657 

immunization, 115 
Swine-plague, 657 
Sycosis parasitaria, 676 
Symbiotes equi of Gerlach, 734 
Symmetrical gangrene, 177 
Sj^mmyelia, 517 
Symptomatic anthrax, 656 

protective inoculations against, 115 
Sympus, 517 
Syncephalus, 585 
Syncope, 16 
Syncytium, 458 
Syndactylism, 519 
Syngamus branchialis, 723 

trachealis, 723 
Synophthalmus, 506 
Synotia, 509 
Syphilides, 633 



Syphilis, bacillus of, 631 
hereditar}^ 636 

transmission to foetus, 64, 638 
Syringomyelia, 53 
Syringomyelocele. 501 

Tabanid^, 735 

Tablet-formed cocci, 540, 541, 559 
Tactile irritability, 103 
Taenia Africana, 710 

coenurus, 710 

cucumerina, 710 

echinococcus, 711 

denticulata, 710 

diminuta, 710 

elliptica, 710 

expansa, 710 

flavapuncta, 710 

mamillana, 710 

marginata, 710 

mediocanellata, 709 

nana, 710 

perfoliata; 710 

plicata, 710 

saginata, 709 

serrata, 710 

solium, 706 
Tail, formation of a, in the human being, 

525 

Talipomanus, 521 

Tapeworms, see also under Tcmia, 705 
Tarichium megaspermum, 678 
Tartar of the teeth, 226 
Tattooing of the skin, 248 
Teeth in dermoid cysts, 481 

supernumerary, 525 
Telangiectasia, 893 

lymphatica, 399 
Temperature, influence of, upon develop- 
ment of bacteria, 543 
Temperatures, high, of the body, 9 

low, of the body, 10 
Tendinous spot, 849 
Teratoid cysts, 473 

tumors, 473 
Teratoma, autochthonous, 480 

bigerminal, 480 

coccygeal, 479, 480, 538 

heterochronous and heterotopous, 474 

monogerminal, 480 

sacral, 475 

of sexual glands, 481, 486 

solid, 483 
Terminal artery, 132 
Testicle, adenocystoma of, 444 

adenorhabdom3^oma of, 485 

angiosarcoma of, 425 

congenital adenocystoma of, 484 

dermoid cysts of, 486 

ectopia of' 520 

retention of, in the abdominal cavity, 
520 

teratoma ta of, 485 
Tetanotoxin, 602 
Tetanus, 601 

antitoxin, 117, 606 
Tetanus-bacillus, 601 



GENERAL INDEX. 



Tetany, thyreoprival, 85 
Texas fever, 696 
Thallophytes, 668 

Thoracic cavity, faulty closure of, 512 
Thoracogastroschisis, 511 
Thoracopagus, 536 
parasiticus, 538 
Threadworms, 720 
Thrombin, 136 

Thrombo-arteritis purulenta, 147 
Thrombo-phlebitis purulenta, 147 
Thrombosis, 134 

sequelae of, 146 
Thrombus, 144 

autochthonous, 144 

induced, 144 

laminated, 137 

mixed, 137 

red, 136 

white, 137 
Thrombus-mole, 497 
Thyreoprival cachexia, 85 

tetany, 85 
Thyroid, angiosarcoma of, 425 

extirpation of, 85 
Thyroiodine, 85 

Tibia, tuberculous disease of. 621 
Tipulidae, 735 
Ticks, 732 
Tinea favosa, 675 

Tissue-implantation, bigerminal, 480 

monogerminal, 480 
Tissue -lesion, 315 
Tissues, restitution of the, 265 
Toes, stunting of, 519 
Tongue, actinomycosis of the, 650 
Tongue- worms, 731 
Tophi, gouty, 225 
Torula-chains, 559 
Toxalbumins, 18, 38, 42, 549 
Toxenzymes, 18 
Toxic substances, 18, 37 
Toxinaemia, 39 
Toxins, 549 
Toxoids, 100 
Toxons, 599 
Toxoses, 100 

Transmissible pathological conditions and 

tendencies, 56 
Transplantation, 305 
Transportation, retrograde, 67 
Traumatic epithelial cysts, 459 

neuroses, 17 
Trematoda, 700 
Trichina spiralis, 726 
Trichocephalus dispar, 726 
Trichomonas intestinalis, 682 

vaginalis, 682 
Trichophyton tonsurans, 676 
Tritotoxin, 599 

Trophoneurotic diseases of the tissues, 78 
Trypanosoma Brucii, 684 

sanguinis, 683 
Tsetse disease, 683 
Tubercle, 609 

solitary, 618 
Tubercles, 'miliary, 616 



Tuberculin, 116, 614 
Tuberculobactericidin, 614 
Tuberculomyces, 613 
Tuberculomycoprotein, 614 
Tuberculosis, 607 

avian, 628 

bacillus, 607 

bovine, 628 

haematogenous miliary, 625 

infection with. 608 
Tube-cocci, 540 
Tumors, 366 

adenocarcinoma, 461 

adenocystoma, 442 

adenoma, 437 

adenosarcoma, 468 

angiosarcoma, 424 

benign and malignant, 378 

cachexia accompanying, 879 

carcinoma, 449 

cavernous, 397 

chloromata, 429 

chondromata, 386 

chordoma, 388 

classification of, 369 

connective-tissue, 367 

cylindroma, 431 

cystic, 442 

cystocarcinoma, 469 

definition of, 366 

dermoid cysts, 473 

desmoid, 3S0 

different varieties, 380 

enchondroma, 386 

endothelioma, 420 

epithelial, 433 

etiology, 371 

fibroma, 380 

fibromyoma, 406 

fibrosarcoma, 415 

glioma, 408 

growth of, by infiltration, 37 
haemangiomata, 393 
histoid, 367 
keloid, 382 
leiomyoma, 404 
lipoma, 384 
lymphangiomata, 399 
malignant, 379 
melanosarcomata, 428 
metastases, 375 
myofibroma, 406 
myoma, 404 
myxochondroma, 383 
myxoma, 382 
myxofibroma, 382 
myxolipoma, 382 
myxosarcoma, 382 
neurofibroma, 411 
neuroglioma gangtiouare, 408 
neuroma, 411 
organoid, 420 
osteoid sarcoma, 430 
osteoma, 389 
^ papilloma, 380 
psammoma, 430 
recurrence of, 378 



760 



GENERAL INDEX. 



Tumors, retrogressive changes iu, 377 

rhabdomyoma, 406 

sarcocarcinoma, 468 

sarcoma, 414 

structure of, 367 

teratoid, 478 
Twin-formations, rudimentary, 480 
Tympanic cavity, cholesteatomata in, 436 
Typhoid fever, bacillus of, 589 

protective inoculations against. 116 

of fowls, 658 
Typhotoxin, 38 
Typhus recurrens, 366 

Udder-inflammations, 580 
Ulceration, tuberculous, 622 
Ulcer, 336 

chronic, 363 

indolent, 363 

serpiginous, 363 
Ulcus atonicum, 363 

callosum, 363 

elevatum hypertrophicum, 368 

indolens, 363 

molle, 607 
Umbilical hernia, 511 
Urachus-cysts, 477 • 
Uraemia, 79 

Urates, deposit of, in gout, 224 

Ureteritis cystica, 690 

Urethra, abnormal narrowness of, 515 

absence of, 515 

atresia of, 515 
Urethritis, gonorrhoeal, 577 
Uric-acid deposits, 224, 228, 280 

infarct, 228 
Urinary calculi, 228 
Urobilin, 236 
Urobilinuria, 236 
Uterus, adenocarcinoma of, 461 

beginning carcinoma of cervix, 455 

myoma of, 404 
Uvula, bifurcation of, 508 

Vaccine, 690 

Vacuoles, 151, 169, 190, 322 
Valves, lesions of, 125 
Valvular thrombus, 144 
Variola, 690 
Vascular naevi, 394 

system, pathological changes in the, 
53 

walls, pathological alterations of, 315 
Vasculitis, proliferating, 350 
Vasomotor nerves, irritation or paralysis 

of, 159 
Vein-stones, 227 
Venous pulsation, 125 



Venous pulse, 125 
Veratrine, poisoning by, 29 
Vermes, 700 
Verruca carnea, 401 

senilis, 434 

vasculosa, 395 
Vertebra3, supernumerary, 525 
Vertebral canal, deficient closure of, 498 
Vesicles, 324, 327 
Vibrio cholerae, 660 

of Metschnikoff, 665 

rugula, 659 

serpens, 659 
Vibrion butyrique, 582 

septique of Pasteur, 602 
Viscera, abnormal positions of, 520 

duplications of, 525 
Visual apparatus, pathological conditions 
of, 55 

Vitelline duct, cyst of, 513 
Vitiligo, 250 
Volatile poisons, 22 

Wandering cells, 319 
Warts, fleshy, 400 

ichthyotic, 434 

senile, 434 

venereal, 262, 362 
Water, effects of lack of, 6 
Weights of different organs, 259 
Whip-infusoria, 681 
Whip-worm, 726 
White gangrene, 176 
Whooping-cough, bacillus of, 597 
Widal-Gruber reaction, 109, 592 
Wolffian body, 529 
Wolf's jaws, 508 
Wood-jack or wood-tick, 732 
Worm-disease of the ox, 659 
Worms, 45, 700 

parasitic, 45, 700 
Worm-disease, 646 
Wound-diphtheritis, 340 
Wound-granulations, 345 
Wound-infection, 48 
Wounds, effects of, 15 

Xanthin calculi, 230 
Xiphopagus, 536 

Yeast-fungi, 668 
Yellow fever, 606 

Zona dermatica, 500 

epithelo-serosa, 500 
Zoogloea, 542 
Zymase, 550 

Zymoid, putrefactive, 41 



